Alzheimer's Assocition International Conference on Alzheimer's Disease (updated diagnostic criteria) 2010 July 10 - 15 Honolulu, Hawaii
I think it's a step forward. small step, but at least it is not a step backward. Most of these type scans have been around for some time, although technology has improved over the years. We have floundered much too long with Alzheimer's and other neurological disease. Just to hear them say they are now going to try and start to _identify_ these cases, as oppose to in the past i.e. only search for nvCJD i.e. UKBSEnvCJD only theory. Maybe, just maybe, a light bulb went off in some of the minds of the ones that matter (prion Gods), and now say something like 'maybe we should start to identify all these potential TSE, including Alzheimer's type dementia, Parkinson's and other neurodegenerative diseases, and regardless of any poential sources. We know now science is leaning towards it's potential to be transmissible, we know there is a common denominator('s?), we just don't have the complete formula to figure it out with yet$ so let's not wait around like we did with the nvCJD and sporadic CJD's debate on the potential for blood and blood products being transmissible, let's not wait around like we did that, until we exposed everyone around the globe, let's not wait around like that, let's ACT NOW, instead of later, regardless.' Let's _indentify_, ACT when something is indentified, act as if it is likely to be Iatrogenic FIRST, then let's prove it's is not, NOT the other way around, like saying it is not transmissible first, acting on that, then taking over 2 decades and finding out it is transmissible. By then it is too late. Let's not sit around and talk about if for over two decades. I know that there has been a blood ban restriction due to CJD, but the USA has failed terribly in it's regulation there from, as with everything esle related to Transmissible Spongiform Encephalopathy regulations. ... just my take.
EMBARGOED FOR RELEASE UNTIL WEDNESDAY, JULY 14, 2010 7:30 am HST / 1:30 pm ET „P
John R. McCarten, et al. Changes In Outpatient Costs Following Screening And Diagnosis Of Cognitive Impairment. (Funded by: Strategic Initiative, Veterans Integrated Service Network 23)
All materials to be presented at the Alzheimer's Association 2010 International Conference on Alzheimer's Disease are embargoed for publication and broadcast until the date and time of presentation at the conference, unless the Alzheimer's Association provides advance written notice of change of date and/or time.
Control #: 10-HT-3470-ALZ O4-04 - Hot Topics 3 (Presentation #O4-04-04; Speaking Time: 7/14/2010 1:45-2:00 PM)
Changes In Outpatient Costs Following Screening And Diagnosis Of Cognitive Impairment
John R. McCarten, M.D.1, Pauline Anderson, MSN2, Michael A. Kuskowski, Ph.D.1, Yvonne Jonk, Ph.D.3, Maurice W. Dysken, M.D.1. 1VA Medical Center, Minneapolis, MN, USA, 2Veterans Integrated Service Network 23, Minneapolis, MN, USA, 3University of Minnesota, Minneapolis, MN, USA. Contact: J Riley McCarten, mccar034@umn.edu Disclosure Block: J.R. McCarten, MN/ND Chapter of the Alzheimer's Association's BOD.
Background: Dementia is a common, costly, and often unrecognized problem in older adults. Early identification and intervention holds the promise of improving care through chronic disease management strategies. We integrated a program of screening, evaluation, and management for cognitive impairment into primary care. Here we report the impact of that program on total and line item outpatient costs.
Methods: The Dementia Demonstration Project (DDP) employed specially trained Advanced Practice Registered Nurses functioning as Dementia Care Coordinators (DCCs) to lead interdisciplinary teams in the identification, evaluation, diagnosis and management of cognitive impairment (CI). Typical primary care clinics were identified at seven VA Medical Centers and the DDP was implemented in those clinics. The DCCs screened eligible veterans (age 70 and older, medically stable, able to comply with the screen, and without a prior diagnosis of CI) using the Mini-Cog at the time of a routine primary care clinic appointment. All patients newly diagnosed with CI, both in DDP and non-DDP PC clinics, who had data available for at least one year before and one year after diagnosis were analyzed. Risk adjusted differences in log transformed outpatient health care utilization and costs were analyzed using the mixed effects Poisson regression and difference-in-differences models.
Results: Of the 8278 veterans screened, 26% failed the screen. A total of 34% of those who failed completed a further evaluation and 95% of this group was found to have CI, including 76% with dementia. Data for one year before and after CI diagnosis were available on 347 DDP patients and 1261 non-DDP patients. Median DDP outpatient care costs declined over 54% (- 2 $5,519) compared with 25% decline (-$1,759) in patients diagnosed in non-DDP clinics. Median number of line-item outpatient costs declined by 53% (-54) in the DDP patients compared to 32% (-21) in non-DDP patients.
Conclusions: Diagnosing cognitive impairment was associated with a decrease in total and line item health care costs in the year following diagnosis compared to the year prior to diagnosis. The decreases were more dramatic in patients who were identified through cognitive screening and subsequently had case management available by a dementia care team.
http://www.alz.org/icad/documents/abstracts/2010_early_detection.pdf
National Institute on Aging and Alzheimer's Association Lead Effort to Update Diagnostic Criteria for Alzheimer's Disease
- News briefing/Q&A: AAICAD 2010, Tuesday, July 13, 2010, 11:45 am-12:45 pm Hawai'i Convention Center, Room 321A, 1801 Kalakaua Avenue, Honolulu -
Honolulu, Hawaii, July 13, 2010 – Scientists at the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) today presented the first draft reports from three workgroups convened by the National Institute on Aging (NIA) and the Alzheimer's Association to update the diagnostic criteria for Alzheimer's disease for the first time in 25 years.
The current criteria for the diagnosis of Alzheimer's were established by a National Institute of Neurological Disorders and Stroke (NINDS)/Alzheimer's Disease and Related Disorders Association (ADRDA) workgroup in 1984. These criteria were almost universally adopted and have been useful; they have survived intact without modification for more than 25 years. However, experts note, the field has evolved to a great extent since then.
"Important scientific discoveries have been made in Alzheimer's, and there have been significant changes in our knowledge and conception of the disease," said Creighton H. Phelps, Ph.D., Director of the Alzheimer's Disease Centers Program, Division of Neuroscience, National Institute on Aging at the National Institutes of Health. "The NIA and the Alzheimer's Association, after consultation with the Alzheimer's scientific and medical community, concluded that the diagnostic criteria may need to be revised to incorporate scientific advances. We decided to convene workgroups to examine the literature and make recommendations."
At AAICAD 2010, leaders of the three workgroups – which covered Alzheimer's disease dementia, mild cognitive impairment (MCI) due to Alzheimer's disease, and preclinical Alzheimer's disease – presented preliminary reports at a special session for initial comment by the Alzheimer's community.
"The proposals would change the 1984 criteria by better reflecting the various stages of the disease and the inclusion of Alzheimer's disease biomarkers," said William Thies, PhD, Chief Medical and Scientific Officer at the Alzheimer's Association. "While the role of biomarkers differs in each of the three stages, much remains to be understood concerning their reliability and validity in diagnosis. This makes it critical that we thoroughly test any new recommendations."
Further input will be solicited by the NIA and the Association through a website launched immediately after the AAICAD presentations at www.alz.org/research/diagnostic_criteria. After that input is incorporated, next steps are publication in a peer-reviewed journal followed by systematic validation through incorporation of the criteria into clinical trials.
"The proposed criteria for Alzheimer's disease dementia must be flexible enough to eventually be used – once they are validated – by both general health care providers without access to neuropsychological testing, advanced imaging, and CSF measures, as well as specialized investigators involved in research or clinical trial studies with access to these measures," said Guy McKhann, MD, of John Hopkins University School of Medicine, who chaired this workgroup.
The Importance of Moving to Earlier Diagnosis
Alzheimer's is thought to begin years, perhaps even decades, before symptoms are noticeable. But there is no single, generally accepted way to identify the disease in its earliest stages – before symptoms are evident.
According to Phelps, earlier detection of people at highest risk for Alzheimer's and those who have the earliest forms of the disease will facilitate finding the right individuals to participate in risk reduction and prevention research studies.
"The NIA and the Alzheimer's Association hope this process of updating and revising the Alzheimer's diagnostic criteria with modern technologies and the latest advances will provide standards that move the field further in the direction of early detection and treatment," Thies said.
Significant Advances in Alzheimer Research Since 1984
Among the most important advances in the Alzheimer's field since the publication of the 1984 NINDS/ADRDA diagnostic criteria are:
•Alzheimer's-driven changes in the brain, as well as the accompanying cognitive deficits, develop slowly over many years with dementia representing the end stage of years of pathology accumulation. At the same time, we know that some people have the brain changes associated with Alzheimer's and yet don't show symptoms of dementia.
•Predictive genes in early onset Alzheimer's indicate that the initial events ultimately leading to both clinical symptoms and pathological brain changes begin with disordered beta amyloid metabolism. •The e4 allele of the APOE gene is well accepted as a major genetic risk factor for late onset Alzheimer's disease, which is defined as onset at 65 or older.
•Biomarkers for Alzheimer's have been developed and are being validated. These fall into several categories:
Biomarkers of beta amyloid pathology, including amyloid PET imaging and levels of beta amyloid in cerebrospinal fluid (CSF).
Biomarkers of neuronal injury, including levels of CSF tau and phospho-tau.
Biomarkers of neuronal dysfunction, including decreased uptake of FDG on PET scans.
Biomarkers of neurodegeneration, including brain atrophy on structural MRI scans. In addition, it has been only in the past decade that a better understanding of the distinctions and overlaps of Alzheimer's with non-Alzheimer's dementias has begun to emerge. Knowledge of the non-Alzheimer's dementias was rudimentary in 1984, and the current diagnostic criteria are vague in defining distinctions between Alzheimer's and the major alternatives. The common co-existence of Alzheimer's and cerebrovascular disease is now appreciated. Much more is known about dementia resulting from Lewy Body disease, and also about Pick's disease and other frontotemporal dementias.
Three Work Group Reports Present New Ideas for Research Criteria and Better Define Early Stages of Alzheimer's Disease
The NIA/Alzheimer's Association working groups were organized around the three stages of Alzheimer's disease that are commonly thought to exist today – pre-clinical Alzheimer's, mild cognitive impairment (MCI) due to Alzheimer's, and Alzheimer's dementia.
•Pre-clinical – The group is laying out a research agenda to identify methods of assessment that may help predict risk for developing the disease. Biomarkers and other clinical assessment tools to identify early cognitive decline are being investigated to establish the presence of Alzheimer's brain changes in people with no overt symptoms and to identify those who may eventually develop the disease.
•Mild cognitive impairment – The group is refining the MCI criteria, which will help to indicate cognitive change before dementia and better differentiate MCI from Alzheimer's. Research is underway to better understand the cognitive changes taking place, how they may relate to biomarkers, and which of these methods best indicate the likelihood of imminent progression to Alzheimer's dementia.
•Alzheimer's dementia – The group is revising the existing criteria for diagnosing Alzheimer's to include possible biomarkers and other assessments that may aid in diagnosis. About AAICAD The Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD) is the world's largest conference of it's kind, bringing together researchers from around the world to report and discuss groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders. As a part of the Alzheimer's Association's research program, AAICAD serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.
About the Alzheimer's Association The Alzheimer's Association is the leading voluntary health organization in Alzheimer care, support and research. Our mission is to eliminate Alzheimer's disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer's.
www.alz.org/icad/
Workgroup members (2 pages)
http://www.alz.org/icad/documents/abstracts/2010_diag.pdf
Contact: Alzheimer's Association Media line: 312.335.4078 E-mail: media@alz.org AAICAD 2010 press room, July 10-15: 1-808-792-6523
http://www.alz.org/icad/2010_release_diagnostic_071310_130pm.asp
Early Detection, Diagnosis & Care Management for People with Dementia May Reduce Healthcare Costs
Honolulu, Hawaii; July 14, 2010 – Early detection, diagnosis and care management for people newly diagnosed with cognitive impairment and dementia reduces outpatient costs by almost 30 percent, according to new research reported today at the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) in Honolulu.
Dementia is loss of memory and other mental abilities severe enough to interfere with daily life. According to the Alzheimer's Association, dementia is a common, costly, and often unrecognized problem in older adults. In order to provide better medical care and outcomes for people with Alzheimer's and other dementias, the conditions must first be detected and diagnosed, and needed care management must be provided.
"Research suggests that when the family of someone who is officially diagnosed with Alzheimer's becomes educated about the disease, and they work together with medical professionals on a care plan, it can reduce the patient's difficult behavioral and psychiatric symptoms," said Maria Carrillo, PhD, Senior Director of Medical and Scientific Relations at the Alzheimer's Association. "It can also lower the family caregiver's anxiety, depression and stress."
Generally, care management in Alzheimer's provides assistance for people with the disease and their families in finding resources, making decisions, and managing stress. For example, a care manager can help families with decisions about in-home health services, or long-term care whether at home or in a nursing facility.
"We see in this study's findings that early diagnosis and case management in dementia may also significantly lower healthcare costs. This could have a reverberating positive impact throughout the entire healthcare system," Carrillo said.
Demonstration Project Shows Early Diagnosis and Care Management Can Lower Costs
The Dementia Demonstration Project (DDP) was an interdisciplinary effort led by the Geriatric Research, Education and Clinic Center at the Minneapolis Veterans (VA) Medical Center. Seven VA Medical Centers took part in the project, which was created to increase detection and diagnosis of dementia in primary care and provide information, support, and care coordination for veterans with newly diagnosed dementia. An Advanced Practice Registered Nurse trained in dementia – the Dementia Care Coordinator – led a dementia care team that became part of a primary care clinic in each of the seven VA Medical Centers participating in the project.
The DDP added a brief, three-item memory test to regularly scheduled primary care visits for veterans age 70 and older without a diagnosis of Alzheimer's or another dementia. Among the 8,278 veterans who received the memory test, 26 percent failed. Thirty-four percent of those who failed the test returned for a comprehensive evaluation; 95 percent of that group were diagnosed with cognitive impairment, including 76 percent with dementia.
In the DDP clinics, following evaluation, the dementia care team met with the patient and family to review the results, discuss the diagnosis, and outline treatment recommendations. Interventions were targeted to the severity of dementia and the specific needs of the patient and their caregivers. Informational material, assistance in identifying needed services, and direct support and training from team members was provided, as needed.
Healthcare costs data for one year before and after diagnosis were available for 347 DDP patients and 1,260 patients from non-DDP clinics in the same VA Medical Centers.
•Veterans diagnosed in the DDP clinics saw their average outpatient healthcare costs decline by about 29 percent (-$1,991) in the year after diagnosis of cognitive impairment compared with the year before diagnosis. •Veterans diagnosed in the non-DDP clinics also saw declines in average outpatient healthcare costs, but not as much (-$406). "In our study, the cost decreases were more dramatic in patients who were identified through cognitive evaluation and who subsequently had case management available by a dementia care team," said J. Riley McCarten, MD, the project's lead physician. He added that the cost of the DDP intervention to the VA was captured in the patient care costs reported.
"The most important goals of the program were making sure that all family members understood the disease and were on the same page, that patients remained physically active and socially engaged, and that caregivers had the support they needed," McCarten said.
About AAICAD The Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD) is the world's largest conference of it's kind, bringing together researchers from around the world to report and discuss groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders. As a part of the Alzheimer's Association's research program, AAICAD serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.
About the Alzheimer's Association The Alzheimer's Association is the leading voluntary health organization in Alzheimer care, support and research. Our mission is to eliminate Alzheimer's disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer's. Visit www.alz.org or call 800-272-3900.
Abstracts (2 pages)
http://www.alz.org/icad/documents/abstracts/2010_early_detection.pdf
Contact: Alzheimer's Association Media line: 312.335.4078 E-mail: media@alz.org AAICAD 2010 press room, July 10-15: 1-808-792-6523
http://www.alz.org/icad/2010_release_early_071410_1230pm.asp
"Hot Topics" from the Alzheimer's Association International Conference on Alzheimer's Disease 2010
- New Alzheimer's Risk Gene May Affect Memory Scores and Brain Atrophy in Middle Age -
- Clinical Trial of Intranasal Insulin Shows Benefits in Alzheimer's and MCI –
- Known Alzheimer's Risk Gene May Change Shape of Brain Deposits -
Honolulu, Hawaii; July 14, 2010 – Last minute scientific submissions to the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) in Honolulu, HI, known as "hot topics," suggest that (1) a newly-discovered risk gene for Alzheimer's may have early impact on memory skills and brain volume, (2) intranasal insulin may be beneficial in Alzheimer's, and (3) beta amyloid deposits in the brains of people with Alzheimer's disease may take different shapes based on a known Alzheimer's risk gene.
Two studies reported at AAICAD 2010 give us more information about the TOMM40 gene – a newly identified risk gene for Alzheimer's. They found that healthy, middle aged people who have the high risk version of TOMM40 (a) did worse on memory tests and (b) had reduced brain volume in two regions affected early in Alzheimer's. A short-term trial of intranasal insulin in Alzheimer's and MCI showed statistically significant benefits on certain tests of memory and functioning, but no changes on some others. In those who showed benefits on memory tests, there were also positive changes in Alzheimer's biomarkers in spinal fluid. Researchers using a new imaging tool suggest that there are different shapes of beta amyloid deposits in the Alzheimer brain based on which version a person has of a well-established Alzheimer's risk gene, known as APOE. This may be especially important because in some recent drug trials the therapy provided benefits in people who had certain types of APOE but were less effective or not effective in others. "These are some of the fantastic findings from this year's AAICAD, full of potential to move the field forward," said William Thies, PhD, Alzheimer's Association Chief Medical and Scientific Officer. "But there is too little happening in the field, and no plan in place from the federal government to stem the massive wave of Alzheimer's coming with the aging of the Baby Boomers."
"Alzheimer's is clearly the #1 public health challenge of the 21st century and research is the only way to solve this problem," Thies added. "There are more than 5 million Americans with the disease and about 11 million caregivers supporting them. Reliable estimates say that by 2050 those numbers could triple. Government must make an investment in Alzheimer research that proves they understand what's at stake – for individuals, families, the healthcare system, and the nation as a whole."
New Risk Gene for Alzheimer's is Associated with Poorer Memory Function and Grey Matter Loss in Middle Aged Persons Without Dementia
The TOMM40 gene has very recently been shown to influence age of onset in Alzheimer's disease. Two studies reported at AAICAD 2010 give us more information about this newly identified risk gene for Alzheimer's; they found that middle aged people without dementia who have the high risk version of the TOMM40 gene did worse on tests of memory and learning and had reduced brain volume in two regions that are often affected early in the course of Alzheimer's.
"These are exciting, initial results, but the exact role that TOMM40 plays in Alzheimer's remains to be determined," said William Thies, PhD, Chief Medical and Scientific Officer at the Alzheimer's Association. "The story of TOMM40 is evolving and may give us new insights into Alzheimer's disease."
"We desperately need to know more about the causes of Alzheimer's, and the factors that affect our risk of getting or not getting the disease. This kind of research will provide more targets for therapies and prevention strategies," Thies said.
In one study, Mark Sager, MD, of the University of Wisconsin Medical School, and colleagues studied a total of 726 people in middle-age with a family history of Alzheimer's from the Wisconsin Registry for Alzheimer's Prevention who were genotyped for TOMM40 and APOE, the latter of which is a well-established risk gene for Alzheimer's. Of these, 129 had the low risk version of TOMM40 and 229 had the high risk version. The average age of the study population was 54.
The researchers found that the group with the high risk version of the TOMM40 gene performed significantly worse on the tests of learning and memory (Rey Auditory Verbal Learning Test) than the group with the low risk version. These results remained significant regardless of APOE gene type.
"The deficits shown by the high risk group are similar to the kinds of changes in memory and learning that are seen in very early Alzheimer's," Sager said. "In this study population, TOMM40 genotyping is allowing us to find evidence of very early Alzheimer's disease at least 20 years before people begin to show the outward symptoms. This is a step forward in Alzheimer's prevention research."
In a second study, Sterling Johnson, PhD, also of the University of Wisconsin School of Medicine and Public Health, and colleagues found that among healthy, middle aged adults (mean age 57) who have the APOE e3/e3 gene type, those with the high risk version of the TOMM40 gene had significantly less gray matter volume in two brain regions affected early in Alzheimer's disease than those with the low risk version of the gene.
According to the researchers, the study suggests that there is a connection between TOMM40 and brain cell loss in people who are relatively young and currently not symptomatic.
"This is the first study to associate TOMM40 to brain imaging in people at risk for Alzheimer's disease," Johnson said. "The brain differences between TOMM40 groups were very similar but less severe that what is observed in full-blown Alzheimer's. It may be that the TOMM40 gene will be a useful measure of Alzheimer's risk in middle-age, but additional research with longitudinal follow-up is needed."
Allen Roses, MD, and colleagues at Duke University first discovered that the TOMM40 gene helped explain differences in age of onset among people with sporadic Alzheimer's disease.
Clinical Trial of Intranasal Insulin Shows Some Benefits in Alzheimer's and MCI
Previous research has strongly suggested that Alzheimer's and diabetes/insulin resistance are closely related. For example, Alzheimer's is associated with reduced brain insulin signaling and low levels of insulin in cerebrospinal fluid (CSF).
"These deficiencies may reduce or eliminate insulin's beneficial roles in the brain," said Suzanne Craft, PhD, of VA Puget Sound Health Care System/University of Washington in Seattle. "We believe that restoring normal insulin function in the brain may provide therapeutic benefits to adults with Alzheimer's. Intranasal administration enables insulin to access brain regions that are compromised in Alzheimer's."
Craft and colleagues had previously shown enhanced cognition and daily functioning in adults with MCI and early Alzheimer's using intranasal insulin treatment for 21 days. This new study expanded the time frame to four months, during which 109 participants with MCI or Alzheimer's received either placebo, or 20 or 40 IU daily intranasal insulin treatment.
The researchers found that in the 20 IU dose group (10 IU twice daily) results on a test of delayed story recall significantly improved compared with those who received placebo, as did functional status measured by the Dementia Severity Rating Scale. Improvements in delayed memory recall persisted for two months after the insulin treatment ended. However, memory and learning on the ADAS-Cog and ability to do activities of daily living measured by the ADCS-ADL scores were unchanged.
For 15 of the insulin-treated participants who agreed to have a spinal tap, improved memory and functional status were associated with an improved Alzheimer's biomarker profile as reflected by a lowered CSF tau/Aß42 ratio.
"These results provide encouraging support for further study of intranasal insulin as a therapy for Alzheimer's," Craft said. "We are currently planning a large, multi-center clinical trial."
New Imaging Compounds for Alzheimer's Protein Deposits in the Brain Show that Different Forms of the APOE Risk Gene Create Different Shapes of Beta Amyloid
A new class of biomarkers has been discovered that can stick to protein structures in the body and emit colors reflecting the different shapes or forms of the proteins. They are called luminescent conjugated oligothiophenes (LCOs) or luminescent conjugated polymers (LCPs). Among other uses, they are currently being employed in test tubes, animal models and autopsied Alzheimer's brains to study the structure of proteins deposits caused by the disease. The new markers bind to the two well-established hallmarks of Alzheimer's – beta amyloid plaques and tau tangles – and glow different colors depending on which forms of the deposits they "stick" to (e.g., plaques often "glow" orange, while tangles "glow" yellowish green).
In this study reported at AAICAD 2010, Sam Gandy, MD, PhD, of Mount Sinai School of Medicine, New York, and colleagues used LCOs/LCPs to investigate the possibility that the shape of brain protein deposits in people with Alzheimer's who have the APOE e4/e4 gene type (highest risk) is different from those having APOE e3/e3 (neutral risk).
Frozen brain sections from people who died with Alzheimer's were stained using two LCPs/LCOs: pentamer formyl thiophene acetic acid (pFTAA) and polythiophene acetic acid (PTAA). Using PTAA, the researchers observed that Alzheimer patients with APOE e4/e4 had core and cerebrovascular amyloid of different shapes, while in people with APOE e3/e3 the two amyloid structures had the same shape. Using pFTAA revealed that tau tangle densities in e4/e4 Alzheimer patients that were apparently greater than those with e3/e3.
"The findings support our hypothesis that APOE genotype changes amyloid structure," Gandy said. "This is important because the different shapes might respond differently to treatments that attempt to clear amyloid deposits from the brain."
In some recent drug trials, the experimental therapy provided benefits in people who had a certain type of the APOE gene (known as e3) but were less or not effective in another type (e4).
LCOs/LCPs were pioneered by Peter Nilsson of the Department of Chemistry, Linköping University, Sweden. The study also involved collaborating teams from Charité – Universitätsmedizin Berlin, Germany (led by Frank Heppner), Washington University, St Louis (led by David Holtzman), and other labs at Mount Sinai (led by Patrick Hof and Dara Dickstein).
About AAICAD The Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD) is the world's largest conference of it's kind, bringing together researchers from around the world to report and discuss groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders. As a part of the Alzheimer's Association's research program, AAICAD serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.
About the Alzheimer's Association The Alzheimer's Association is the leading voluntary health organization in Alzheimer care, support and research. Our mission is to eliminate Alzheimer's disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer's. Visit www.alz.org or call 800-272-3900.
Abstracts (6 pages)
14, 2010, 6:30-7:30 am, Hawai’i Convention Center, 1801 Kalakaua Avenue, Honolulu, Room 321A.
Mark A. Sager, et al. TOMM40 Variable Length Polymorphism Is Associated With Memory Function In Asymptomatic Middle-aged Persons. (Funded by: National Institute on Aging, Helen Bader Foundation, Extendicare Foundation)
Sterling C. Johnson, et al. TOMM40 Is Associated With Gray Matter Volume In Middle-aged Persons With Apoe e3/e3 Genotype. (Funded by: National Institute on Aging, Department of Veterans Affairs)
Suzanne Craft, et al. Intranasal Insulin- And Biomarker-associated Improvement In Memory And Functional Status In Mild Cognitive Impairment And Alzheimer's Disease: Results Of A Randomized, Double-blind, Placebo-controlled Pilot Trial. (Funded by: Department of Veterans Affairs, National Institute on Aging)
Hannah Brautigam, Sam Gandy, et al. New Conformation-Sensing Imaging Compounds Distinguish Protein Deposits In APOE e3/e3 Alzheimer’s Patients From That In APOE e4/e4 Alzheimer’s Patients. (Funded by: National Institutes of Health, Cure Alzheimer’s Fund, European Union FP7 HEALTH (Project LUPAS), German Research Foundation, Knut and Alice Wallenberg Foundation, Swedish Foundation for Strategic Research)
All materials to be presented at the Alzheimer's Association 2010 International Conference on Alzheimer's Disease are embargoed for publication and broadcast until the date and time of presentation at the conference, unless the Alzheimer's Association provides advance written notice of change of date and/or time.
Control #: 10-HT-3354-ALZ
TOMM40 Variable Length Polymorphism Is Associated With Memory Function In Asymptomatic Middle-aged Persons Mark A. Sager, M.D.1, Asenath La Rue, Ph.D.1, Sterling C. Johnson, Ph.D.1, Ann M. Saunders, Ph.D.2, Allen D. Roses, M.D.2, Rebecca Koscik, Ph.D.1, Erin Jonaitis, Ph.D.1, Michael W. Lutz, Ph.D.2, Sanjay Asthana, M.D.1, Robert C. Green, Ph.D., M.Ph.3, Bruce P. Hermann, Ph.D.1.
1UW Medical School-Madison, Madison, WI, USA, 2Duke University, Durham, NC, USA, 3Boston University, Boston, MA, USA. Contact Email: masager@wisc.edu
Disclosure Block: M.A. Sager, None.
Background: A TOMM40 polymorphism, a variable length intronic poly T repeat (rs10524523), has been shown to influence age of Alzheimer’s disease (AD) onset. In this study, we tested the hypothesis that subjects homozygous for TOMM40 short poly T sequences <21 (SPT) would show better performance on measures of learning and memory than those who were homozygous for longer poly T sequences =21 (LPT) in middle-aged subjects with a family history of AD.
Methods: The study population includes 726 middle-aged asymptomatic persons enrolled in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) who had been genotyped for APOE and 2 TOMM40. A total of 129 were homozygous for SPT sequences <21 (low risk) and 229 were homozygous for LPT sequences =21 (high risk). Study groups were defined by TOMM40 genotyping based on the length of the poly T sequences regardless of APOE genotype. Serial position profiles and total learning on the Rey Auditory Verbal Learning Test (AVLT) were compared between groups controlling for age, gender and education.
Results: The mean age of the study population was 54 and 69% were female. There were no significant age, gender or education differences between SPT and LPT groups. The two TOMM40 groups differed significantly in total words learned on the AVLT (p = .012) with the LPT TOMM40 group remembering fewer words. There were significant differences in the serial position curve with significantly poorer recall from the primacy region on the AVLT (p = .001). Nineteen percent of the SPT group had an APOE e4 compared with 55% of the LPT group. When APOE genotype (e4 carrier vs. non-carrier) was added to the model, TOMM40 remained significant on both measures.
Conclusions: Longer TOMM40 poly T sequence length was associated with differences in memory and learning that are seen in early AD. These changes were seen in middle-aged asymptomatic persons, suggesting that TOMM40 genotyping may prove useful in stratifying persons at different levels of AD risk in studies of pre-symptomatic AD. The role that TOMM40 plays in AD pathogenesis and its relationship to APOE genotype as a genetic risk factor for AD remain to be determined.
All materials to be presented at the Alzheimer's Association 2010 International Conference on Alzheimer's Disease are embargoed for publication and broadcast until the date and time of presentation at the conference, unless the Alzheimer's Association provides advance written notice of change of date and/or time.
Control #: 10-HT-3432-ALZ O4-03 - Hot Topics 2 (Presentation #O4-03-04; Speaking Time: 7/14/2010 1:45-2:00 PM)
TOMM40 Is Associated With Gray Matter Volume In Middle-aged Persons With APOE e3/e3 Genotype
Sterling C. Johnson, Ph.D.1,2, Asenath La Rue, Ph.D.1, Bruce P. Hermann, Ph.D.1, Guofan Xu, Ph.D.1, Rebecca L. Koscik, Ph.D.1, Erin M. Jonaitas, Ph.D.1, Barbara B. Bendlin, Ph.D.1,2, Allen D. Roses, MD3, Ann M. Saunders, Ph.D.3, Michael W. Lutz, Ph.D.3, Sanjay Asthana, MD1,2, Robert C. Green, MD4, Mark A. Sager, MD1. 1University of Wisconsin, Madison, WI, USA, 2Wm. S. Middleton Veterans Hospital, Madison, WI, USA, 3Duke University, Durham, NC, USA, 4Boston University, Boston, MA, USA. Contact Email: scj@medicine.wisc.edu Disclosure Block: S.C. Johnson, None
Background: Apolipoprotein E (APOE) genotypes are associated with variable risk of developing late onset Alzheimer’s disease (LOAD), with APOE e4 having higher risk. A variable poly-T length polymorphism at rs10524523, within intron 6 of the TOMM40 gene has very recently been shown to influence age of onset in LOAD, where very long poly-T length was associated with earlier disease onset, and short poly-T length associated with later onset. In this study, we tested the hypothesis that brain changes antedating symptomatic LOAD may be associated with this TOMM40 polymorphism.
Methods: Among healthy APOE e3 homozygous adults (mean age 57), we compared those homozygous for very long (VL/VL; n=33) TOMM40 poly-T lengths (who are presumably at 3 higher risk) to those homozygous for short (S/S; n=37) poly-T lengths on structural brain imaging. Voxel-based morphometry was used to assess gray matter volume using the software SPM8. Gray matter probability maps were entered into a voxel-wise ANCOVA where Age and Intracranial volume were covariates
Results: Results were that the VL/VL TOMM40 group had significantly less gray matter volume in the ventral posterior cingulate and precuneus, a region of the brain affected early in LOAD.
Conclusions: To our knowledge, this is the first study to associate TOMM40 523 genotypes to brain imaging in people at risk for AD. These findings suggest that the group with very long TOMM40 poly-T lengths may be experiencing incipient LOAD-related cognitive and brain changes. The participants in this study are being followed over time to determine genetic and other factors that predict cognitive decline and dementia 4 5
All materials to be presented at the Alzheimer's Association 2010 International Conference on Alzheimer's Disease are embargoed for publication and broadcast until the date and time of presentation at the conference, unless the Alzheimer's Association provides advance written notice of change of date and/or time.
Control #: 10-HT-3439-ALZ O4-04 - Hot Topics 3 (Presentation #O4-04-01; Speaking Time: 7/14/2010 1:00-1:15 PM)
Intranasal Insulin- And Biomarker-associated Improvement In Memory And Functional Status In Mild Cognitive Impairment And Alzheimer's Disease: Results Of A Randomized, Double-blind, Placebo-controlled Pilot Trial
Suzanne Craft, PhD1, Laura D. Baker, PhD1, Thomas J. Montine, MD, PhD2, Jing Zhang, MD, PhD2, G. Stennis Watson, PhD1, Stephen Plymate, MD1, Elaine Tsai, MD1, Maureen Callaghan, MD1, James Leverenz, MD1, Brooke Gerton, MD1, Emily Trittschuh, PhD1. 1University of Washington/VA Puget Sound, Seattle, WA, USA, 2University of Washington, Seattle, WA, USA. Contact Email: scraft@u.washington.edu Disclosure Block: S. Craft, None.
Background: Alzheimer’s disease (AD) is associated with reduced brain insulin signaling and low CSF insulin levels. These deficiencies may abrogate insulin’s role in synaptic maintenance, Aß regulation, and other mechanisms related to AD pathogenesis. Restoring normal insulin function in brain may thus provide therapeutic benefit to adults with AD. Intranasally administered insulin follows extracellular pathways to the brain, bypassing the periphery and blood brain barrier, and accessing the CNS within 15 minutes. Previously, we showed that cognition and daily function are enhanced following intranasal insulin treatment for 21 days in adults with amnestic mild cognitive impairment (MCI) and early AD.
Methods: Participants with MCI or AD (n=109) received either placebo, or 20 or 40 IU daily intranasal insulin treatment for four months. ADAS-Cog/MCI and delayed story recall scores were primary outcome measures and were administered at baseline, at 2 and 4 months during treatment, and 2 months after treatment cessation. Secondary measures of functional status included the Dementia Severity Rating Scale (DSRS) and Alzheimer Disease Cooperative Study Activity of Daily Living Scale (ADCS-ADL). A subset of participants (n=23) received lumbar punctures at baseline and after 4 months of treatment. For the intent-to-treat analysis, outcome measures for each dose group were compared to the placebo group with repeated measures analysis of variance.
Results: Delayed story recall improved in the 20 IU dose group compared with placebo (p=0.0201), as did functional status reflected by DSRS (p=0.0054). Improved delayed memory persisted 2 months after insulin treatment ended (p=0.0209). ADAS-Cog and ADCS-ADL scores were unchanged. The 40 IU dose group had improved daily function relative to placebo on the DSRS (p=0.0095), but no differences in cognition. For CSF biomarker analysis, the two insulin dose groups were combined to increase power. For insulin-treated participants (n=15), improved delayed memory and functional status were associated with an improved AD biomarker profile as reflected by a lowered CSF tau/Aß42 ratio (Spearman rhos=-.52 and .53, ps<0.05). n="8;">.90).
Conclusions: These results provide strong support for further investigation of intranasal insulin as a therapeutic approach for patients with MCI and AD.
All materials to be presented at the Alzheimer's Association 2010 International Conference on Alzheimer's Disease are embargoed for publication and broadcast until the date and time of presentation at the conference, unless the Alzheimer's Association provides advance written notice of change of date and/or time.
Control #: 10-HT-3369-ALZ
O4-04 - Hot Topics 3 (Presentation #O4-04-06; Speaking Time: 7/14/2010 2:15-2:30 PM)
6
New Conformation-Sensing Imaging Compounds Distinguish Protein Deposits In APOE e3/e3 Alzheimer’s Patients From That In APOE e4/e4 Alzheimer’s Patients
Hannah Brautigam, BS Psychology1, Thérese Klingstedt, MS Biomedicine2, Stefan Prokop, MD3, David M. Holtzman, MD4, Frank L. Heppner, MD3, Vahram Haroutunian, PhD1, Dara L. Dickstein, PhD1, Patrick R. Hof, MD1, Peter R. Nilsson, PhD2, Sam Gandy, MD, PhD1,5. 1Mount Sinai School of Medicine, New York, NY, USA, 2Linköping University, Linköping, Sweden, 3Charité-Universitäsmedizin Berlin, Berlin, Germany, 4Washington University School of Medicine, St. Louis, MO, USA, 5James J. Peters VA Medical Center, Bronx, NY, USA. Contact Email: hannah.brautigam@mssm.edu; samgandy@gmail.com
Disclosure Block: H. Brautigam, None.
Background: A novel class of biomarkers, luminescent conjugated oligothiophenes (LCOs) or luminescent conjugated polymers (LCPs), has been designed to intercalate into proteinaceous structures and emit spectra reflecting discrete conformation states. LCOs/LCPs have enabled the discrimination of prion strain isotypes and are currently being employed in vitro and in vivo to study the structure of aggregated proteins in Alzheimer’s disease (AD); LCOs/LCPs bind to amyloid beta (Aß) deposits and neurofibrillary tangles (NFTs) in histological brain sections of AD patients, emitting spectra related to the conformation(s) of these deposits. In addition to Aß, apolipoprotein E (APOE) is a component of human brain amyloid, and the APOE e4 allele is the major genetic risk factor for sporadic AD. We employed LCOs/LCPs to investigate the possibility that the conformation of brain protein deposits in AD patients having e4/e4 alleles differed from deposits in AD patients having e3/e3 alleles.
Methods: Frozen brain sections were analyzed from pairs of AD patients matched for age, gender, CDR score, and duration of disease; only APOE genotype, e4/e4 or e3/e3, differed between pairs. Adjacent sections from each pair were stained using two LCPs/LCOs: pentamer formyl thiophene acetic acid (pFTAA) and polythiophene acetic acid (PTAA). Fluorescence spectra from tissue sections were recorded with an LSM 510 META confocal laser scanning microscope, and spectral processing was achieved with an LSM Image browser.
Results: Using PTAA, we observed that AD patients with e4/e4 exhibited a different conformational spectrum for core and cerebrovascular amyloid whereas their respective matched e3/e3 pair exhibited indistinguishable conformational spectra between the two amyloid structures. pFTAA, sensitive for different conformations for Aß and NFTs, revealed NFT densities in e4/e4 AD patients that were apparently greater than those in e3/e3 AD patients.
Conclusions: The observation that PTAA core amyloid and cerebrovascular amyloid spectra distinguish the amyloid deposits of APOE e4/e4 from APOE e3/e3 AD patients supports the hypothesis that APOE genotype modulates amyloid structure. pFTAA holds promise as an especially sensitive reagent for visualizing NFTs. LCOs/LCPs show great potential as research tools for the study of proteinopathies, including the pathogenesis of sporadic AD and possibly the influence of APOE genotype.
# # #
http://www.alz.org/icad/documents/abstracts/2010_hot_topics.pdf
Contact: Alzheimer's Association Media line: 312.335.4078 E-mail: media@alz.org AAICAD 2010 press room, July 10-15: 1-808-792-6523
http://www.alz.org/icad/2010_release_hot_071410_1230pm.asp
ICAD Press ReleasesMore News> 07/14/10 "Hot Topics" from the Alzheimer's Association International Conference on Alzheimer's Disease 2010 07/14/10 Early Detection, Diagnosis & Care Management for People with Dementia May Reduce Healthcare Costs 07/14/10 New Research Advances from the Alzheimer's Association International Conference on Alzheimer's Disease 2010 07/13/10 National Institute on Aging and Alzheimer's Association Lead Effort to Update Diagnostic Criteria for Alzheimer's Disease 07/13/10 Alzheimer's Disease may Increase Risk of Anemia and Seizures 07/13/10 Four New Research Studies Describe Experimental Immunotherapies for Alzheimer's 07/12/10 Alzheimer's Association Launches TrialMatch™ – First-of-its-Kind Clinical Trials Matching Service in Alzheimer's National News 07/15/10 Fighting Alzheimer's disease -ABC World News Tonight 07/15/10 Insulin via nasal spray shows benefit in people with Alzheimer's -USA Today 07/15/10 Early diagnosis of Alzheimer's yields savings -The Wall Street Journal
http://www.alz.org/icad/
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognised the public sensitivity of these findings and intend to report them in their proper context. This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.
2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed", As the report emphasises the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.
What are the implications for public health?
3. The route of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process, Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.
92/11.4/1.1
4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required" before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.
J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832
92/11.4/1.2
http://collections.europarchive.org/tna/20081106170650/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight
Date: 5 January 1993
Copies:
Dr Metters
Dr Skinner
Dr Pickles
Dr Morris
Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of B amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1
http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Wednesday, April 14, 2010
Food Combination and Alzheimer Disease Risk A Protective Diet
http://betaamyloidcjd.blogspot.com/2010/04/food-combination-and-alzheimer-disease.html
Wednesday, March 31, 2010
Neurobiology of Disease Molecular Cross Talk between Misfolded Proteins in Animal Models of Alzheimer's and Prion Diseases
http://betaamyloidcjd.blogspot.com/2010/03/neurobiology-of-disease-molecular-cross.html
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
P03.139
Cellular Prion Protein Regulates the ß-Secretase Cleavage of the Alzheimer's Amyloid Precursor Protein
Hooper, NM1; Parkin, ET1; Watt, NT1; Baybutt, H2; Manson, J2; Hussain, I3; Turner, AJ1 1University of Leeds, Institute of Molecular and Cellular Biology, UK; 2Roslin Institute, Neuropathogenesis Unit, UK; 3GlaxoSmithKline, Neurodegeneration Research, UK
Background: The normal cellular function of the prion protein (PrP), the causative agent of the transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease (CJD) in humans, remains enigmatic. Several studies have reported combinations of Alzheimer's Disease (AD) and CJD neuropathology and the Val/Met129 polymorphism in the PrP gene has been identified as a risk factor for early-onset AD, leading to speculation that there may be some pathogenic connection between these two neurodegenerative conditions. The amyloid ß (Aß) peptides that cause AD are derived from the amyloid precursor protein (APP) through sequential proteolytic cleavage by the ß-secretase (BACE1) and the g-secretase complex.
Aim: As both APP and PrP are cleaved by zinc metalloproteases of the ADAM family, we investigated whether PrP alters the proteolytic processing of APP.
Results: Here we show that expression of PrP in SH-SY5Y cells dramatically downregulated the cleavage of APP by BACE1 and reduced the secretion of Aß peptides into the conditioned medium by >92%. Conversely, siRNA reduction of endogenous PrP in N2a cells led to an increase in secreted Aß. Furthermore, levels of Aß were significantly increased in the brains of PrP null mice as compared with wild type mice. Two mutants of PrP, PG14 and A116V, that are associated with familial human prion diseases, did not inhibit the BACE1 cleavage of APP. To investigate whether the Val/Met129 polymorphism in human PrPC would alter the production of Aß, brains from mice with the human PrP gene with MM or VV 129 genotypes were analysed. In the MM mice there was a significant increase in Aß in the brains as compared with the VV mice. In the brains of two strains (79A and 87V) of scrapie-infected mice there was a significant increase in Aß peptides as compared to uninfected mice.
Conclusions: Together these data reveal a novel function for PrP in regulating the processing of APP through inhibition of BACE1. The increase in APP processing in cells expressing disease-associated forms of PrP and in scrapie-infected brains raises the possibility that the increase in Aß may contribute to the neurodegeneration observed in prion diseases. Funded by the Medical Research Council of Great Britain.
P03.140
Prion Protein Regulates the ß-Secretase Cleavage of the Alzheimer's Amyloid Precursor Protein through Interaction with Glycosaminoglycans
Griffiths, HH; Parkin, ET; Watt, NT; Turner, AJ; Hooper, NM University of Leeds, Institute of Molecular and Cellular Biology, UK
Background: Proteolytic processing of the amyloid precursor protein (APP) by ßsecretase, BACE1, is the initial step in the production of the amyloid ß (Aß) peptide which is involved in the pathogenesis of Alzheimer's disease. We have shown that the cellular prion protein (PrP) inhibits the cleavage of APP by BACE1 in cell and animal models.
Aim: To investigate the mechanism by which PrP inhibits the action of BACE1.
Results: Neither PrPdeltaGPI, which is not membrane attached, nor PrP-CTM, which is anchored by a transmembrane domain and is excluded from cholesterol-rich lipid rafts, reduced cleavage of APP, suggesting that to inhibit the BACE1 cleavage of APP PrP has to be localised to lipid rafts. Coimmunoprecipitation experiments demonstrated that PrP physically interacts with BACE1. However, PrP did not alter the activity of BACE1 towards a fluorogenic peptide substrate nor perturb the dimerisation of BACE1. Using constructs of PrP lacking either the octapeptide repeats or the 4 residues KKRP at the N-terminus of the mature protein (PrPdeltaN), we demonstrate that the KKRP sequence but not the octapeptide repeats, is essential for regulating the BACE1 cleavage of APP. As the KKRP sequence is known to participate in glycosaminoglycan (GAG) binding, we confirmed that PrPdeltaN did not bind to immobilised heparin. Addition of heparin to SH-SY5Y cells increased the amount of APP cleaved by BACE1 in a concentration-dependent manner and reduced the amount of BACE1 coimmunoprecipitated with PrP, suggesting that GAGs are required for PrP to interact with BACE1 and inhibit APP processing. Of a range of GAGs, including dextran sulphate, hyaluronic acid and chondroitin sulphate, investigated there was complete correlation between those that could restore BACE1 cleavage of APP in PrP expressing cells and those that bound PrP.
Conclusion: These data suggest a possible mechanism by which PrP regulates the ßcleavage of APP is through the N-terminus of PrP interacting via GAGs with one or more of the heparin binding sites on BACE1 within a subset of cholesterol-rich lipid rafts, thereby restricting access of BACE1 to APP. Funded by the Medical Research Council of Great Britain.
P04.37
Comparison of the Neuropsychological Profile of Patients with Sporadic Creutzfeldt-Jakob Disease and Patients with Alzheimer's
Krzovska, M1; Cepek, L1; Ratzka, P2; Döhlinger, S3; Uttner, I1; Wolf, Stefanie4; Irle, Eva4; Mollenhauer, Brit5; Kretzschmar, Hans A.6; Riepe, Matthias7; v. Arnim, Christine1; Otto, Markus1 1University of Ulm, Germany; 2Department of Neurology, Germany; 3University of Goettingen, Germany; 4University of Goettingen, Germany; 5Elena Klinik, Germany; 6LMU, Germany; 7University of Berlin, Germany
Background:To evaluate the neuropsychological profile of sCJD we administered the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) in order to determine if and how the sCJD-Subgroups (Met/Met, Met/Val, Val/Val) have different results in the item analysis of the ADAS-cog. Furthermore, we studied how the scores differ from that of patients with Alzheimer's disease (AD).
Methods:33 sCJD patients (11 with definite CJD and 22 with probable CJD) underwent neuropsychological testing with the ADAS-cog and Mini Mental State Exam (MMSE). Of these 31 were genotyped at the Codon 129 (11 Val/Val, 18 Met/Val and 2 Met/Met). The patients were matched in regards to sex and total ADAS-cog score with AD patients. The scores of the 11 ADAS-cog items were compared between the sCJD and the AD groups as well as between the sCJD-subgroups Met/Val and Val/Val and the AD group.
Results:The ADAS-cog total score of the sCJD and AD groups was 22.6+/- 6.5, respectively. Regarding the single Item scores of the sCJD patient group and the AD patient group, there were statistically significant differences in the Items Constructional praxis, Word-finding difficulty in spontaneous speech and Spoken language ability. When comparing the sCJD subtypes with each other no statistically significant difference was found in the items.
Conclusion: In the speech and constructional praxis there is indication of greater impairment in sCJD patients in general when compared with AD patients. A disturbance of the speech appears to be an important characteristic of the Met/Val and Val/Val subtypes of sCJD, and should therefore be the focus of special attention in future neuropsychological studies.
http://www.neuroprion.com/pdf_docs/conferences/prion2007/abstract_book.pdf
http://www.neuroprion.org/resources/pdf_docs/conferences/prion2007/abstract_book.pdf
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease
http://betaamyloidcjd.blogspot.com/2008/04/re-association-between-deposition-of.html
Saturday, March 22, 2008
10 Million Baby Boomers to have Alzheimer's in the coming decades 2008 Alzheimer's disease facts and figures
http://betaamyloidcjd.blogspot.com/2008/03/association-between-deposition-of-beta.html
Monday, January 4, 2010
Rising Tide: The Impact of Dementia in Canada Huge wave of dementia cases coming, warns report
http://betaamyloidcjd.blogspot.com/2010/01/rising-tide-impact-of-dementia-in.html
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Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility
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Could cases of protease sensitive prionopathy (PSP) be missed by conventional tests which, in all other TSEs, rely on the resistance of the prion protein in the nervous system that accompanies disease to digestion by protease enzymes?
Can we develop reliable methods for removing and detecting protein on re-usable surgical instruments?
SNIP...
FULL TEXT ;
Monday, October 12, 2009
SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens TSE 8 October 2009
http://bse-atypical.blogspot.com/2009/10/seac-science-and-technology-committees.html
Sunday, June 7, 2009
ALZHEIMER'S DISEASE IS TRANSMISSIBLE
http://betaamyloidcjd.blogspot.com/2009/06/alzheimers-disease-is-transmissible.html
http://betaamyloidcjd.blogspot.com/
TSS
Sunday, July 18, 2010
Friday, May 7, 2010
Spouses of Dementia Sufferers Have a Six-Fold Increased Risk of Dementia Onset
Spouses of Dementia Sufferers Have a Six-Fold Increased Risk of Dementia Onset:
Husbands Appear at Higher Risk Than Wives
April 30th, 2010
Strictly Embargoed Until 00.01 Hours (EST) Wednesday, May 5, 2010
Contact: Jennifer Beal +44 (0) 1243 770633 Medicalnews@wiley.com
Spouses of Dementia Sufferers Have a Six-Fold Increased Risk of Dementia Onset
Husbands Appear at Higher Risk Than Wives Older married adults whose spouse has dementia are at significantly higher risk for developing dementia themselves, compared to similar older married adults whose spouse never develops dementia. This is the key finding of a study published today in the Journal of the American Geriatrics Society.
Informal dementia caregiving for a spouse is a natural marital obligation, and spousal caregivers often report positive feelings toward caregiving, yet it is difficult, requiring time, energy and usually physical exertion. Dementia caregivers have been shown to provide more assistance, and to report more personal sacrifices and stress, than those who care for physically-impaired elderly without dementia. While there are many published studies showing that dementia caregivers are at higher risk for health problems and depression, none have examined risk for dementia in the caregiver.
2,442 subjects (1,221 married couples) aged 65 and older from Northern Utah, USA, without dementia at onset were studied for up to 12 years to monitor for onset of dementia in husbands, wives or both. During this time, 125 cases of dementia only in the husband were diagnosed, 70 only in the wife, and 30 where both spouses were diagnosed (60 people).
The researchers, led by Dr. Maria Norton of Utah State University, USA, adjusted for socioeconomic status, a significant predictor of many health-related outcomes including dementia to control for shared environmental exposures that might influence risk for dementia in both spouses.
The results showed that incident dementia was significantly associated with older age, and having a spouse with dementia. Participants with a spouse who developed dementia were at a six times increased risk of developing dementia, net of the effect of age, gender, APOE genotype, and socioeconomic status, with higher risk in men (11.9) than women (3.7).
“Future studies are needed to determine how much of this association is due to caregiver stress compared to a shared environment,” said Norton. “On the positive side, the majority of these individuals, with spouses who develop dementia, did not themselves develop dementia, therefore more research is needed to explore which factors distinguish those who are more vulnerable.”
“Given the significant public health concern of Alzheimer’s disease and other dementias, and the upcoming shift in population age composition, continued research into the causes of dementia is urgent,” concluded Norton. __________________________________________________________________
This study is published in the issue of the Journal of the American Geriatrics Society. Media wishing to receive a PDF of this article may contact medicalnews@wiley.com
Full citation: Norton et al; Increased Risk of Dementia When Spouse Has Dementia? The Cache County Study; The Journal of the American Geriatrics Society, May 2010
About the Author: Dr. Maria Norton is based at Utah State University, USA. To arrange an interview with Dr. Norton, please contact Tim Vitale at Utah State University’s Public Relations office on tim.vitale@usu.edu or +1 435-797-1356.
About the Journal: The Journal of the American Geriatrics Society is a comprehensive and reliable source of monthly research and information about common diseases and disorders of older adults. The journal is published by Wiley-Blackwell on behalf of the American Geriatrics Society. For more information, please visit www.blackwellpublishing.com/jgs.
About Wiley-Blackwell: Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world’s leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or www.interscience.wiley.com.
Modified On: May 5th, 2010
http://www.americangeriatrics.org/press/id:665
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
http://betaamyloidcjd.blogspot.com/2010/03/neurobiology-of-disease-molecular-cross.html
http://betaamyloidcjd.blogspot.com/2010/04/food-combination-and-alzheimer-disease.html
Wednesday, April 14, 2010
Food Combination and Alzheimer Disease Risk A Protective Diet
http://betaamyloidcjd.blogspot.com/2010/04/food-combination-and-alzheimer-disease.html
TSE & HOUNDS
GAH WELLS (very important statement here...TSS)
HOUND STUDY
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.
http://web.archive.org/web/20010305222642/www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf
76 pages on hound study;
http://web.archive.org/web/20030327022236/http://www.bseinquiry.gov.uk/files/sc/seac16/tab04.pdf
I thought that in Britain dogs had contracted BSE, but perhaps not.
not so fast here;
The spongiform changes were not pathognomonic (ie. conclusive proof) for prion disease, as they were atypical, being largely present in white matter rather than grey matter in the brain and spinal cord. However, Tony Scott, then head of electron microscopy work on TSEs, had no doubt that these SAFs were genuine and that these hounds therefore must have had a scrapie-like disease. I reviewed all the sections myself (original notes appended) and although the pathology was not typical, I could not exclude the possibility that this was a scrapie-like disorder, as white matter vacuolation is seen in TSEs and Wallerian degeneration was also present in the white matter of the hounds, another feature of scrapie.
38.I reviewed the literature on hound neuropathology, and discovered that micrographs and descriptive neuropathology from papers on 'hound ataxia' mirrored those in material from Robert Higgins' hound survey. Dr Tony Palmer (Cambridge) had done much of this work, and I obtained original sections from hound ataxia cases from him. This enabled me provisionally to conclude that Robert Higgins had in all probability detected hound ataxia, but also that hound ataxia itself was possibly a TSE. Gerald Wells confirmed in 'blind' examination of single restricted microscopic fields that there was no distinction between the white matter vacuolation present in BSE and scrapie cases, and that occurring in hound ataxia and the hound survey cases.
39.Hound ataxia had reportedly been occurring since the 1930's, and a known risk factor for its development was the feeding to hounds of downer cows, and particularly bovine offal. Circumstantial evidence suggests that bovine offal may also be causal in FSE, and TME in mink. Despite the inconclusive nature of the neuropathology, it was clearly evident that this putative canine spongiform encephalopathy merited further investigation.
40.The inconclusive results in hounds were never confirmed, nor was the link with hound ataxia pursued. I telephoned Robert Higgins six years after he first sent the slides to CVL. I was informed that despite his submitting a yearly report to the CVO including the suggestion that the hound work be continued, no further work had been done since 1991. This was surprising, to say the very least.
41.The hound work could have provided valuable evidence that a scrapie-like agent may have been present in cattle offal long before the BSE epidemic was recognised. The MAFF hound survey remains unpublished.
Histopathological support to various other published MAFF experiments
42.These included neuropathological examination of material from experiments studying the attempted transmission of BSE to chickens and pigs (CVL 1991) and to mice (RVC 1994).
http://www.bseinquiry.gov.uk/witness/htm/stat067.htm
It was thought likely that at least some, and probably all, of the cases in zoo animals were caused by the BSE agent. Strong support for this hypothesis came from the findings of Bruce and others (1994) ( Bruce, M.E., Chree, A., McConnell, I., Foster, J., Pearson, G. & Fraser, H. (1994) Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and species barrier. Philosophical Transactions of the Royal Society B 343, 405-411: J/PTRSL/343/405 ), who demonstrated that the pattern of variation in incubation period and lesion profile in six strains of mice inoculated with brain homogenates from an affected kudu and the nyala, was similar to that seen when this panel of mouse strains was inoculated with brain from cattle with BSE. The affected zoo bovids were all from herds that were exposed to feeds that were likely to have contained contaminated ruminant-derived protein and the zoo felids had been exposed, if only occasionally in some cases, to tissues from cattle unfit for human consumption.
snip...
NEW URL ;
http://collections.europarchive.org/tna/20080102174910/http://www.bseinquiry.gov.uk/files/ws/s324.pdf
SEE LETTER FROM MAFF TO ME IN 2005 ABOUT THE HOUND STUDY ;
2005
DEFRA Department for Environment, Food & Rural Affairs
Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk
GTN: FAX:
Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518
21 November 2001
Dear Mr Singeltary
TSE IN HOUNDS
Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.
As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.
Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.
Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less
critical. For more details see- http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address.
Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK
You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any suspect SE in dogs for further investigation. To date there has never been positive identification of a TSE in a dog.
I hope this is helpful
Yours sincerely 4
HUGH MCDONAGH BSE CORRESPONDENCE SECTION
======================================END...TSS
WHAT ABOUT THOSE STUMBLING, STAGGERING, AND BLIND DOGS, the old dog syndrome, just another spontaneous event ???
The signs of canine cognitive dysfunction syndrome or "old dog syndrome" commonly seen in dogs are: lose of house training increased barking or whining increased anxiety or fear signs disorientation-appearing lost or confused,getting stuck behind furniture or in corners, walking in circles, becoming forgetful,walking aimlessly,staring into space, repetitious or compulsive behavior change in sleep patterns-up at night, sleep all day
lack of responsiveness other changes,may not recognize you, their name,may become more docile, more aggressive.. You can liken it to human senility. An article at the petcenter says "CDS is not "normal aging". A number of pathophysiological changes are suspected to play a role in its development. These include: * deposition of amyloid plaques in the cerebral cortex and hippocampal part of the brain * alterations in neurotransmitters, including dopamine * increased levels of monoamine oxidase B (MAOB) in the brain * increased levels of free radicals L-DEPRENYL HYDROCHLORIDE SELEGILINE HYDROCHLORIDE,BRAND NAME: ANIPRYL OR ELDEPRYL is used to help treat canine cognitive dysfunction by increasing brain concentrations of the neurotransmitter dopamine. Hopefully you can see a difference in a month or so. If you don't see a difference in the first month, your vet might tell you to try two pills a day for the next month. ANIPRYL doesn't work for all dogs. A great writeup on L-DEPRENYL can be found at
http://www.petsinfo.org/elderlydogs1.html
"One third of canine CD patients respond extremely well to treatment with deprenyl by regaining their youthful vigor; another one third respond reasonably well; and one third do not respond at all (perhaps there is a variant of CD with different neuropathology). The bottom line is that for any dog that is slowing down to the point that problems become apparent, treatment with deprenyl is the logical route once other organic causes for reduced mental function have been ruled out. Here is a write up on selegline " Selegiline has immune-system-boosting and anti-neurodegenerative effects. ....
Taken consistently in low doses, selegiline tends to extend the life-expectancy of rats by some 20%; enhances drive, libido and endurance; and independently improves cognitive performance in Alzheimer's patients and in some healthy normals. It is used successfully to treat canine cognitive dysfunction syndrome (CDS) in dogs...Selegiline protects the brain's dopamine cells from oxidative stress. " Some also use alpha lipoic acid and r-lipoic acid. powerful antioxidants to help slow down canine cognitive dysfunction. There is a dog food that is rich in antioxidants for CDS but I am assuming if you supplement with your own antioxidants you don't have to worry if your dog likes the food or not. I know my dog Hammy has become very picky and at least if I pill him, I know he is getting his antioxidants.
http://www.thensome.com/cds.htm
Doggie Dementia
Does 14-year-old Fido get lost in his own back yard?
Does he not respond when you call his name?
Does he generally seem confused?
According to Pulse, the official magazine of the Southern California Veterinary Medical Association, just as humans in the 21st Century are living longer, so is man’s best friends—more than 7.3 million dogs in the United States are age 10 or older. And with age dogs become prone to the same age-related diseases as their human companions, including dementia.
A disease of old age affects dogs and humans alike
Kazzy, a 17-year-old Lhasa Apso, is one of the 60 percent of dogs aged 11 to 15 who suffer from one or more symptoms of canine cognitive dysfunction syndrome (CDS), also known to veterinarians as doggie dementia. "He used to be the most incredible watchdog," says his owner, Olivia Feldman-Rich. "But he’s not like that anymore. He’s quite bewildered."
Experts like Dr. Maritza Perez, a veterinarian at West Orange (NJ) Animal Hospital, say that confusion is one of the four major signs of CDS (see sidebar). Dr. Perez says dogs may "pace around in circles, get stuck behind furniture, or they don’t know where the back door is anymore."
Often the most distressing sign of CDS is that, like human patients with Alzheimer’s disease, your pet seems to forget you and your family. "A lot of people notice that when you walk in the door, and this dog that was happy to see you doesn’t get up off the couch or off the floor to greet you," says Dr. Perez. "And he doesn’t come anymore when you call him."
These symptoms, coupled with others debilitating diseases affecting older dogs, such as arthritis, all add up to a serious loss in quality of life for your canine friend. The American Veterinary Medical Association reports that some 500,000 dogs are put to sleep each year because of CDS.
Researchers say that deposits of beta-amyloid plaques in brain tissues are likely to play a role in CDS. These plaques build up and eventually inhibit transmission of the brain’s neural signals. Still, the recognized symptoms of CDS are behavioral, so a diagnosis is exclusionary, meaning it is arrived at only after all other physical and neurological causes are ruled out.
No cure yet, but relief for some dogs
Dr. Perez with a 14 year-old beagle who is on Anipryl.
While scientists search for a permanent cure for CDS, there is one treatment currently FDA-approved for CDS. Selegiline hydrochloride, whose brand name is Anipryl, may give some dogs relief from its symptoms. Researchers speculate that Anipryl works by increasing levels of dopamine, a neurotransmitter. Other treatments are currently being investigated, including diets high in anti-oxidants as well as a new drug, Adrafinil, in one Canadian study.
Dr. Perez says that Anipryl does cause an improvement in many dogs with CDS, meaning relief from at least one of the common symptoms. "We have lots of animals on it and it does work," she says. But it’s not a sure thing—Dr. Perez tried it on her own dog with no effect.
Feldman-Rich is debating putting Kazzy on Anipryl. "I’m hoping that it will give a little more balance to his life and make him a little more aware that he’s still here and we’re still here for him," she says. "I always told him that he couldn’t leave me too soon, and he’s definitely kept up his end of it, but I’d definitely like for him to feel a little more like he’s part of the family."
by Debra Utacia Krol
http://www.sciencentral.com/articles/view.php3?article_id=218391360&cat=1_6
SEE CJD IN MAN AND HIS CAT ;
[Image] Research letters Volume 352, Number 9134 [Image] 3 October 1998 [Previous] [Next]
[Image][Image]
Simultaneous occurrence of spongiform encephalopathy in a man and his cat in Italy
[Image]
Gianluigi Zanusso, Ettore Nardelli, Anna Rosati, GianMaria Fabrizi, Sergio Ferrari, Antonella Carteri, Franco De Simone, Nicola Rizzuto, Salvatore Monaco
Transmissible spongiform encephalopathies (TSE) encompass inherited, acquired, and sporadic mammalian neurological disorders, and are characterised by the conversion of the cellular prion protein (PrP) in an insoluble and protease-resistant isoform (PrPres). In human TSE, four types of PrPres have been identified according to size and glycoform ratios, which may represent different prion strains. Type-1 and type-2 PrPres are associated with sporadic Creutzfeldt-Jakob disease (CJD), type 3 with iatrogenic CJD, and type 4 with variant CJD.1,2 There is evidence that variant CJD is caused by the bovine spongiform encephalopathy (BSE)-prion strain.2-4 The BSE strain has been identified in three cats with feline spongiform encephalopathy (FSE), a prion disease which appeared in 1990 in the UK.5 We report the simultaneous occurrence of sporadic CJD in a man and a new variety of FSE in his cat.
A 60-year-old man, with no unusual dietary habits, was admitted in November, 1993, because of dysarthria, cerebellar ataxic gait, visual agnosia, and myoclonus. An electroencephalogram (EEG) showed diffuse theta-delta activity. A brain magnetic resonance imaging scan was unremarkable. 10 days later, he was speechless and able to follow only simple commands. Repeat EEGs showed periodic triphasic complexes. 2 weeks after admission, he was mute, akinetic, and unable to swallow. He died in early January, 1994.
His 7-year-old, neutered, female shorthaired cat presented in November, 1993, with episodes of frenzy, twitching of its body, and hyperaesthesia. The cat was usually fed on canned food and slept on its owner's bed. No bites from the cat were recalled. In the next few days, the cat became ataxic, with hindquarter locomotor dysfunction; the ataxia got worse and there was diffuse myoclonus. The cat was killed in mid-January, 1994.
No pathogenic mutations in the patient's PrP gene were found. The patient and the cat were methionine homozygous at codon 129. Histology of the patient's brain showed neocortical and cerebellar neuronal loss, astrocytosis, and spongiosis (figure A). PrP immunoreactivity showed a punctate pattern and paralleled spongiform changes (figure B). The cat's brain showed mild and focal spongiosis in deeper cortical layers of all four lobes (figure C), vacuolated cortical neurons (figure D), and mild astrogliosis. The cerebellar cortex and the dentate nucleus were gliosed. Immunoreactive PrP showed a punctate pattern in neocortex, allocortex, and caudate nucleus (figure E). Western blot analysis of control and affected human and cat brain homogenates showed 3 PrP bands of 27-35 kDa. After digestion with proteinase K and deglycosylation, only samples from the affected patient and cat showed type-1 PrPres, with PrP glycoform ratios comparable to those observed in sporadic CJD1 (details available from author).
[Image]
Microscopic sections of patient and cat brains
A: Occipital cortex of the patient showing moderate spongiform degeneration and neuronal loss (haematoxylin and eosin) and B: punctate perineuronal pattern of PrP immunoreactivity; peroxidase immunohistochemistry with monoclonal antibody 3F4. C: cat parietal cortex showing mild spongiform degeneration (haematoxylin and eosin).D: vacuolated neurons (arrow, haematoxylin and eosin), E: peroxidase immunohistochemistry with antibody 3F4 shows punctate perineuronal deposition of PrP in temporal cortex.
This study shows a spatio-temporal association between human and feline prion diseases. The clinical features of the cat were different from previously reported cases of FSE which were characterised by gradual onset of behavioural changes preceding locomotor dysfunction and ataxia.5 Neuropathological changes were also at variance with the diffuse spongiosis and vacuolation of brainstem neurons, seen in FSE.5 The synaptic pattern of PrP deposition, similar in the cat and in the patient, was atypical for a BSE-related condition. Evidence of a new type of FSE was further provided by the detection of a type-1 PrPres, other than the BSE-associated type 4.2 Taken together, our data suggest that the same agent strain of sporadic CJD was involved in the patient and in his cat.
It is unknown whether these TSE occurred as the result of horizontal transmission in either direction, infection from an unknown common source, or the chance occurrence of two sporadic forms.
1 Parchi P, Castellani R, Capellari S, et al. Molecular basis of phenotypic variablity in sporadic Creutzfeldt-Jakob disease. Ann Neurol 1996; 39: 767-78 [PubMed].
2 Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF. Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature 1996; 383: 685-90 [PubMed].
3 Bruce ME, Will RG, Ironside JW, et al. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 1997; 389: 498-501 [PubMed].
4 Hill AF, Desbruslais M, Joiner S, et al. The same prion strain causes vCJD and BSE. Nature 1997; 389: 448-50 [PubMed].
5 Pearson GR, Wyatt JM, Henderson JP, Gruffydd-Jones TJ. Feline spongiform encephalopathy: a review. Vet Annual 1993; 33: 1-10.
------------------------------------------------------------------------ Sezione di Neurologie Clinica, Dipartimento di Scienze Neurologiche e della Visione, Università di Verona, Policlinico Borgo Roma, 37134 Verona, Italy (S Monaco; e mail rizzuto@Gorgorna.univr.it); and Istituto Zooprofilattico Sperimentale della Lombardia e dell' Emilia, Brescia
=======================================
Terry S. Singeltary Sr. wrote:
######## Bovine Spongiform Encephalopathy #########
Greetings list members,
ODD that some FELINE in Italy seem to have this same or maybe very similar phenotype of TSE;
In October 1998 the simultaneous occurrence of spongiform encephalopathy in a man and his pet cat was reported. The report from Italy noted that the cat did not display the same clinical features as FSE cases previously seen. Indeed, the presence of a new type of FSE was suggested. The man was diagnosed as having sporadic CJD, and neither case (man nor cat) appeared to be affected by a BSE-related condition.
http://www.defra.gov.uk/animalh/bse/bse-science/level-4-othertses.html
-------- Original Message --------
Subject: FDA BSE Update - Pet Food from Canadian Manufacturer & MAD DOG DATA
Date: Tue, 27 May 2003 08:07:58 -0500
From: "Terry S. Singeltary Sr."
To: Bovine Spongiform Encephalopathy
Statement
FOR IMMEDIATE RELEASE Statement May 26, 2003
Media Inquiries: 301-827-6242 Consumer Inquiries: 888-INFO-FDA
FDA BSE Update - Pet Food from Canadian Manufacturer
The Food and Drug Administration (FDA) has learned from the government of Canada that rendered material from a Canadian cow that last week tested positive for bovine spongiform encephalopathy (BSE, also known as mad cow disease ) may have been used to manufacture pet food, specifically dry dog food, some of which was reported to have been shipped to the United States. The Canadian government prevented the BSE positive cow from being processed for human food. Therefore, consumers can be assured that their food does not contain any remnants of the BSE positive cow.
It is also important to stress that there is no scientific evidence to date that dogs can contract BSE or any similar disease. In addition there is no evidence that dogs can transmit the disease to humans.
FDA notified the U.S. pet food firm, The Pet Pantry International, of Carson City, Nevada, when FDA learned that the pet food that the firm received may have included rendered material from the BSE positive cow. The manufacturer of the pet food is Champion Pet Food, Morinville, Alberta. Even though there is no known risk to dogs from eating this dog food, as a prudent measure to help assure that the U.S. stays BSE free The Pet Pantry International is asking its customers who may have purchased the suspect product to hold it for pickup by the distributor so that the dog food will not mistakenly be mixed into cattle or other feeds if any of the dog food is discarded or otherwise not used to feed dogs. The suspect dog food was produced by Champion Pet Food between February 4, 2003, and March 12, 2003.
The Pet Pantry products were packaged in 50 lb bags, distributed to franchises around the country, and sold by home delivery only. There was no retail distribution of the product. Consumers purchase Pet Pantry products by phone or email orders. The product is then delivered by the nearest franchisee directly to the consumer s home.
The product subject to this notification includes Maintenance Diet labeled with a use by date of 17FEB04 and Beef with Barley with a use by date of 05MAR04 . Consumers who have purchased dog food from The Pet Pantry since February of this year are asked to check their present supplies and see if any match the description of the product being removed. If so, consumers are asked to contact The Pet Pantry at 1-800-381-7387 for further information on how to return the product to The Pet Pantry for proper disposal. Consumers are asked not to destroy or discard the product themselves. The Pet Pantry will also use its sales records to contact consumers who purchased the affected product.
FDA is working closely with the Pet Pantry International to assure for proper disposal of the recovered product.
FDA will continue to provide updates on this case of BSE in Canada as additional information becomes available.
http://www.fda.gov/bbs/topics/NEWS/2003/NEW0910.html
It was thought likely that at least some, and probably all, of the cases in zoo animals were caused by the BSE agent. Strong support for this hypothesis came from the findings of Bruce and others (1994) ( Bruce, M.E., Chree, A., McConnell, I., Foster, J., Pearson, G. & Fraser, H. (1994)
Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and species barrier.
Philosophical Transactions of the Royal Society B 343, 405-411: J/PTRSL/343/405 ), who demonstrated that the pattern of variation in incubation period and lesion profile in six strains of mice inoculated with brain homogenates from an affected kudu and the nyala, was similar to that seen when this panel of mouse strains was inoculated with brain from cattle with BSE. The affected zoo bovids were all from herds that were exposed to feeds that were likely to have contained contaminated ruminant-derived protein and the zoo felids had been exposed, if only occasionally in some cases, to tissues from cattle unfit for human consumption.
snip...
http://collections.europarchive.org/tna/20080102174910/http://www.bseinquiry.gov.uk/files/ws/s324.pdf
cases have been reported in domestic cats), are characterised by long asymptomatic incubation periods followed by progressive symptoms and signs of degeneration of the brain, leading eventually to death.
http://www.bsereview.org.uk/download/draft_2.pdf
PET FOODS MAD CATS AND MAD DOGS BSE/TSEs
worse still, there is serious risk the media could get to hear of such a meeting...
snip...
Crushed heads (which inevitably involve brain and spinal cord material) are used to a limited extent but will also form one of the constituent raw materials of meat and bone meal, which is used extensively in pet food manufacturer...
http://collections.europarchive.org/tna/20080102163540/http://www.bseinquiry.gov.uk/files/yb/1989/03/17004001.pdf
2. The Parliamentary Secretary said that he was concerned about the possibility that countries in which BSE had not yet been detected could be exporting raw meat materials (in particular crushed heads) contaminated with the disease to the UK for use in petfood manufacture...
snip...
YOU explained that imported crushed heads were extensively used in the petfood industry...
http://collections.europarchive.org/tna/20080102154438/http://www.bseinquiry.gov.uk/files/yb/1989/04/14001001.pdf
In particular I do not believe one can say that the levels of the scrapie agent in pet food are so low that domestic animals are not exposed...
http://collections.europarchive.org/tna/20081105230259/http://www.bseinquiry.gov.uk/files/yb/1989/04/24003001.pdf
BSE IN PETFOOD
1. The Secretary asked on 19 April whether I was content with the advice in para 3 of the record of the meeting on 17 March with the Parliamentary Secretary (Mr Thompson). The simple answer is ''not entirely''.
2. On occasions, material obtained from slaughterhouses will be derived from sheep affected with scrapie or cattle that may be incubating BSE for use in petfood manufacture. Some of this material must be classified as high risk since it contains brain, spinal cord, spleen or lymphatic glands.
http://collections.europarchive.org/tna/20090505233052/http://www.bseinquiry.gov.uk/files/yb/1989/05/03007001.pdf
Meldrum's notes on pet foods and materials used
http://collections.europarchive.org/tna/20081105230323/http://www.bseinquiry.gov.uk/files/yb/1989/05/16001001.pdf
http://collections.europarchive.org/tna/20080102200123/http://www.bseinquiry.gov.uk/files/yb/1989/05/16002001.pdf
IN CONFIDENCE CJD TO CATS...
It should be noted that under experimental conditions cats succumb to an encephalopathy after intracerebral inoculation of material derived from patients affected with Creutzfeldt-Jakob Disease.
http://collections.europarchive.org/tna/20080103005226/http://www.bseinquiry.gov.uk/files/yb/1989/05/18002001.pdf
Confidential BSE and __________________
3. I have thought very hard about whether the Branch should carry out a similar exercise with meat and meat products for human foods. On balance I do NOT think we should undertake it, but a final decision has not been taken and you may wish to discuss this further. ...
http://web.archive.org/web/20030509205351/http://www.bseinquiry.gov.uk/files/yb/1989/05/22012001.pdf
full text ;
http://caninespongiformencephalopathy.blogspot.com/
http://betaamyloidcjd.blogspot.com/
Wednesday, February 24, 2010
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America 14th
ICID International Scientific Exchange Brochure -
http://transmissiblespongiformencephalopathy.blogspot.com/2010/02/transmissible-spongiform-encephalopathy.html
Transmissible Spongiform Encephalopathy
http://transmissiblespongiformencephalopathy.blogspot.com/
Monday, April 5, 2010
Update on Feed Enforcement Activities to Limit the Spread of BSE April 5, 2010
http://madcowfeed.blogspot.com/2010/04/update-on-feed-enforcement-activities.html
TSS
Husbands Appear at Higher Risk Than Wives
April 30th, 2010
Strictly Embargoed Until 00.01 Hours (EST) Wednesday, May 5, 2010
Contact: Jennifer Beal +44 (0) 1243 770633 Medicalnews@wiley.com
Spouses of Dementia Sufferers Have a Six-Fold Increased Risk of Dementia Onset
Husbands Appear at Higher Risk Than Wives Older married adults whose spouse has dementia are at significantly higher risk for developing dementia themselves, compared to similar older married adults whose spouse never develops dementia. This is the key finding of a study published today in the Journal of the American Geriatrics Society.
Informal dementia caregiving for a spouse is a natural marital obligation, and spousal caregivers often report positive feelings toward caregiving, yet it is difficult, requiring time, energy and usually physical exertion. Dementia caregivers have been shown to provide more assistance, and to report more personal sacrifices and stress, than those who care for physically-impaired elderly without dementia. While there are many published studies showing that dementia caregivers are at higher risk for health problems and depression, none have examined risk for dementia in the caregiver.
2,442 subjects (1,221 married couples) aged 65 and older from Northern Utah, USA, without dementia at onset were studied for up to 12 years to monitor for onset of dementia in husbands, wives or both. During this time, 125 cases of dementia only in the husband were diagnosed, 70 only in the wife, and 30 where both spouses were diagnosed (60 people).
The researchers, led by Dr. Maria Norton of Utah State University, USA, adjusted for socioeconomic status, a significant predictor of many health-related outcomes including dementia to control for shared environmental exposures that might influence risk for dementia in both spouses.
The results showed that incident dementia was significantly associated with older age, and having a spouse with dementia. Participants with a spouse who developed dementia were at a six times increased risk of developing dementia, net of the effect of age, gender, APOE genotype, and socioeconomic status, with higher risk in men (11.9) than women (3.7).
“Future studies are needed to determine how much of this association is due to caregiver stress compared to a shared environment,” said Norton. “On the positive side, the majority of these individuals, with spouses who develop dementia, did not themselves develop dementia, therefore more research is needed to explore which factors distinguish those who are more vulnerable.”
“Given the significant public health concern of Alzheimer’s disease and other dementias, and the upcoming shift in population age composition, continued research into the causes of dementia is urgent,” concluded Norton. __________________________________________________________________
This study is published in the issue of the Journal of the American Geriatrics Society. Media wishing to receive a PDF of this article may contact medicalnews@wiley.com
Full citation: Norton et al; Increased Risk of Dementia When Spouse Has Dementia? The Cache County Study; The Journal of the American Geriatrics Society, May 2010
About the Author: Dr. Maria Norton is based at Utah State University, USA. To arrange an interview with Dr. Norton, please contact Tim Vitale at Utah State University’s Public Relations office on tim.vitale@usu.edu or +1 435-797-1356.
About the Journal: The Journal of the American Geriatrics Society is a comprehensive and reliable source of monthly research and information about common diseases and disorders of older adults. The journal is published by Wiley-Blackwell on behalf of the American Geriatrics Society. For more information, please visit www.blackwellpublishing.com/jgs.
About Wiley-Blackwell: Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world’s leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or www.interscience.wiley.com.
Modified On: May 5th, 2010
http://www.americangeriatrics.org/press/id:665
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
http://betaamyloidcjd.blogspot.com/2010/03/neurobiology-of-disease-molecular-cross.html
http://betaamyloidcjd.blogspot.com/2010/04/food-combination-and-alzheimer-disease.html
Wednesday, April 14, 2010
Food Combination and Alzheimer Disease Risk A Protective Diet
http://betaamyloidcjd.blogspot.com/2010/04/food-combination-and-alzheimer-disease.html
TSE & HOUNDS
GAH WELLS (very important statement here...TSS)
HOUND STUDY
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.
http://web.archive.org/web/20010305222642/www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf
76 pages on hound study;
http://web.archive.org/web/20030327022236/http://www.bseinquiry.gov.uk/files/sc/seac16/tab04.pdf
I thought that in Britain dogs had contracted BSE, but perhaps not.
not so fast here;
The spongiform changes were not pathognomonic (ie. conclusive proof) for prion disease, as they were atypical, being largely present in white matter rather than grey matter in the brain and spinal cord. However, Tony Scott, then head of electron microscopy work on TSEs, had no doubt that these SAFs were genuine and that these hounds therefore must have had a scrapie-like disease. I reviewed all the sections myself (original notes appended) and although the pathology was not typical, I could not exclude the possibility that this was a scrapie-like disorder, as white matter vacuolation is seen in TSEs and Wallerian degeneration was also present in the white matter of the hounds, another feature of scrapie.
38.I reviewed the literature on hound neuropathology, and discovered that micrographs and descriptive neuropathology from papers on 'hound ataxia' mirrored those in material from Robert Higgins' hound survey. Dr Tony Palmer (Cambridge) had done much of this work, and I obtained original sections from hound ataxia cases from him. This enabled me provisionally to conclude that Robert Higgins had in all probability detected hound ataxia, but also that hound ataxia itself was possibly a TSE. Gerald Wells confirmed in 'blind' examination of single restricted microscopic fields that there was no distinction between the white matter vacuolation present in BSE and scrapie cases, and that occurring in hound ataxia and the hound survey cases.
39.Hound ataxia had reportedly been occurring since the 1930's, and a known risk factor for its development was the feeding to hounds of downer cows, and particularly bovine offal. Circumstantial evidence suggests that bovine offal may also be causal in FSE, and TME in mink. Despite the inconclusive nature of the neuropathology, it was clearly evident that this putative canine spongiform encephalopathy merited further investigation.
40.The inconclusive results in hounds were never confirmed, nor was the link with hound ataxia pursued. I telephoned Robert Higgins six years after he first sent the slides to CVL. I was informed that despite his submitting a yearly report to the CVO including the suggestion that the hound work be continued, no further work had been done since 1991. This was surprising, to say the very least.
41.The hound work could have provided valuable evidence that a scrapie-like agent may have been present in cattle offal long before the BSE epidemic was recognised. The MAFF hound survey remains unpublished.
Histopathological support to various other published MAFF experiments
42.These included neuropathological examination of material from experiments studying the attempted transmission of BSE to chickens and pigs (CVL 1991) and to mice (RVC 1994).
http://www.bseinquiry.gov.uk/witness/htm/stat067.htm
It was thought likely that at least some, and probably all, of the cases in zoo animals were caused by the BSE agent. Strong support for this hypothesis came from the findings of Bruce and others (1994) ( Bruce, M.E., Chree, A., McConnell, I., Foster, J., Pearson, G. & Fraser, H. (1994) Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and species barrier. Philosophical Transactions of the Royal Society B 343, 405-411: J/PTRSL/343/405 ), who demonstrated that the pattern of variation in incubation period and lesion profile in six strains of mice inoculated with brain homogenates from an affected kudu and the nyala, was similar to that seen when this panel of mouse strains was inoculated with brain from cattle with BSE. The affected zoo bovids were all from herds that were exposed to feeds that were likely to have contained contaminated ruminant-derived protein and the zoo felids had been exposed, if only occasionally in some cases, to tissues from cattle unfit for human consumption.
snip...
NEW URL ;
http://collections.europarchive.org/tna/20080102174910/http://www.bseinquiry.gov.uk/files/ws/s324.pdf
SEE LETTER FROM MAFF TO ME IN 2005 ABOUT THE HOUND STUDY ;
2005
DEFRA Department for Environment, Food & Rural Affairs
Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk
GTN: FAX:
Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518
21 November 2001
Dear Mr Singeltary
TSE IN HOUNDS
Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.
As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.
Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.
Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less
critical. For more details see- http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address.
Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK
You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any suspect SE in dogs for further investigation. To date there has never been positive identification of a TSE in a dog.
I hope this is helpful
Yours sincerely 4
HUGH MCDONAGH BSE CORRESPONDENCE SECTION
======================================END...TSS
WHAT ABOUT THOSE STUMBLING, STAGGERING, AND BLIND DOGS, the old dog syndrome, just another spontaneous event ???
The signs of canine cognitive dysfunction syndrome or "old dog syndrome" commonly seen in dogs are: lose of house training increased barking or whining increased anxiety or fear signs disorientation-appearing lost or confused,getting stuck behind furniture or in corners, walking in circles, becoming forgetful,walking aimlessly,staring into space, repetitious or compulsive behavior change in sleep patterns-up at night, sleep all day
lack of responsiveness other changes,may not recognize you, their name,may become more docile, more aggressive.. You can liken it to human senility. An article at the petcenter says "CDS is not "normal aging". A number of pathophysiological changes are suspected to play a role in its development. These include: * deposition of amyloid plaques in the cerebral cortex and hippocampal part of the brain * alterations in neurotransmitters, including dopamine * increased levels of monoamine oxidase B (MAOB) in the brain * increased levels of free radicals L-DEPRENYL HYDROCHLORIDE SELEGILINE HYDROCHLORIDE,BRAND NAME: ANIPRYL OR ELDEPRYL is used to help treat canine cognitive dysfunction by increasing brain concentrations of the neurotransmitter dopamine. Hopefully you can see a difference in a month or so. If you don't see a difference in the first month, your vet might tell you to try two pills a day for the next month. ANIPRYL doesn't work for all dogs. A great writeup on L-DEPRENYL can be found at
http://www.petsinfo.org/elderlydogs1.html
"One third of canine CD patients respond extremely well to treatment with deprenyl by regaining their youthful vigor; another one third respond reasonably well; and one third do not respond at all (perhaps there is a variant of CD with different neuropathology). The bottom line is that for any dog that is slowing down to the point that problems become apparent, treatment with deprenyl is the logical route once other organic causes for reduced mental function have been ruled out. Here is a write up on selegline " Selegiline has immune-system-boosting and anti-neurodegenerative effects. ....
Taken consistently in low doses, selegiline tends to extend the life-expectancy of rats by some 20%; enhances drive, libido and endurance; and independently improves cognitive performance in Alzheimer's patients and in some healthy normals. It is used successfully to treat canine cognitive dysfunction syndrome (CDS) in dogs...Selegiline protects the brain's dopamine cells from oxidative stress. " Some also use alpha lipoic acid and r-lipoic acid. powerful antioxidants to help slow down canine cognitive dysfunction. There is a dog food that is rich in antioxidants for CDS but I am assuming if you supplement with your own antioxidants you don't have to worry if your dog likes the food or not. I know my dog Hammy has become very picky and at least if I pill him, I know he is getting his antioxidants.
http://www.thensome.com/cds.htm
Doggie Dementia
Does 14-year-old Fido get lost in his own back yard?
Does he not respond when you call his name?
Does he generally seem confused?
According to Pulse, the official magazine of the Southern California Veterinary Medical Association, just as humans in the 21st Century are living longer, so is man’s best friends—more than 7.3 million dogs in the United States are age 10 or older. And with age dogs become prone to the same age-related diseases as their human companions, including dementia.
A disease of old age affects dogs and humans alike
Kazzy, a 17-year-old Lhasa Apso, is one of the 60 percent of dogs aged 11 to 15 who suffer from one or more symptoms of canine cognitive dysfunction syndrome (CDS), also known to veterinarians as doggie dementia. "He used to be the most incredible watchdog," says his owner, Olivia Feldman-Rich. "But he’s not like that anymore. He’s quite bewildered."
Experts like Dr. Maritza Perez, a veterinarian at West Orange (NJ) Animal Hospital, say that confusion is one of the four major signs of CDS (see sidebar). Dr. Perez says dogs may "pace around in circles, get stuck behind furniture, or they don’t know where the back door is anymore."
Often the most distressing sign of CDS is that, like human patients with Alzheimer’s disease, your pet seems to forget you and your family. "A lot of people notice that when you walk in the door, and this dog that was happy to see you doesn’t get up off the couch or off the floor to greet you," says Dr. Perez. "And he doesn’t come anymore when you call him."
These symptoms, coupled with others debilitating diseases affecting older dogs, such as arthritis, all add up to a serious loss in quality of life for your canine friend. The American Veterinary Medical Association reports that some 500,000 dogs are put to sleep each year because of CDS.
Researchers say that deposits of beta-amyloid plaques in brain tissues are likely to play a role in CDS. These plaques build up and eventually inhibit transmission of the brain’s neural signals. Still, the recognized symptoms of CDS are behavioral, so a diagnosis is exclusionary, meaning it is arrived at only after all other physical and neurological causes are ruled out.
No cure yet, but relief for some dogs
Dr. Perez with a 14 year-old beagle who is on Anipryl.
While scientists search for a permanent cure for CDS, there is one treatment currently FDA-approved for CDS. Selegiline hydrochloride, whose brand name is Anipryl, may give some dogs relief from its symptoms. Researchers speculate that Anipryl works by increasing levels of dopamine, a neurotransmitter. Other treatments are currently being investigated, including diets high in anti-oxidants as well as a new drug, Adrafinil, in one Canadian study.
Dr. Perez says that Anipryl does cause an improvement in many dogs with CDS, meaning relief from at least one of the common symptoms. "We have lots of animals on it and it does work," she says. But it’s not a sure thing—Dr. Perez tried it on her own dog with no effect.
Feldman-Rich is debating putting Kazzy on Anipryl. "I’m hoping that it will give a little more balance to his life and make him a little more aware that he’s still here and we’re still here for him," she says. "I always told him that he couldn’t leave me too soon, and he’s definitely kept up his end of it, but I’d definitely like for him to feel a little more like he’s part of the family."
by Debra Utacia Krol
http://www.sciencentral.com/articles/view.php3?article_id=218391360&cat=1_6
SEE CJD IN MAN AND HIS CAT ;
[Image] Research letters Volume 352, Number 9134 [Image] 3 October 1998 [Previous] [Next]
[Image][Image]
Simultaneous occurrence of spongiform encephalopathy in a man and his cat in Italy
[Image]
Gianluigi Zanusso, Ettore Nardelli, Anna Rosati, GianMaria Fabrizi, Sergio Ferrari, Antonella Carteri, Franco De Simone, Nicola Rizzuto, Salvatore Monaco
Transmissible spongiform encephalopathies (TSE) encompass inherited, acquired, and sporadic mammalian neurological disorders, and are characterised by the conversion of the cellular prion protein (PrP) in an insoluble and protease-resistant isoform (PrPres). In human TSE, four types of PrPres have been identified according to size and glycoform ratios, which may represent different prion strains. Type-1 and type-2 PrPres are associated with sporadic Creutzfeldt-Jakob disease (CJD), type 3 with iatrogenic CJD, and type 4 with variant CJD.1,2 There is evidence that variant CJD is caused by the bovine spongiform encephalopathy (BSE)-prion strain.2-4 The BSE strain has been identified in three cats with feline spongiform encephalopathy (FSE), a prion disease which appeared in 1990 in the UK.5 We report the simultaneous occurrence of sporadic CJD in a man and a new variety of FSE in his cat.
A 60-year-old man, with no unusual dietary habits, was admitted in November, 1993, because of dysarthria, cerebellar ataxic gait, visual agnosia, and myoclonus. An electroencephalogram (EEG) showed diffuse theta-delta activity. A brain magnetic resonance imaging scan was unremarkable. 10 days later, he was speechless and able to follow only simple commands. Repeat EEGs showed periodic triphasic complexes. 2 weeks after admission, he was mute, akinetic, and unable to swallow. He died in early January, 1994.
His 7-year-old, neutered, female shorthaired cat presented in November, 1993, with episodes of frenzy, twitching of its body, and hyperaesthesia. The cat was usually fed on canned food and slept on its owner's bed. No bites from the cat were recalled. In the next few days, the cat became ataxic, with hindquarter locomotor dysfunction; the ataxia got worse and there was diffuse myoclonus. The cat was killed in mid-January, 1994.
No pathogenic mutations in the patient's PrP gene were found. The patient and the cat were methionine homozygous at codon 129. Histology of the patient's brain showed neocortical and cerebellar neuronal loss, astrocytosis, and spongiosis (figure A). PrP immunoreactivity showed a punctate pattern and paralleled spongiform changes (figure B). The cat's brain showed mild and focal spongiosis in deeper cortical layers of all four lobes (figure C), vacuolated cortical neurons (figure D), and mild astrogliosis. The cerebellar cortex and the dentate nucleus were gliosed. Immunoreactive PrP showed a punctate pattern in neocortex, allocortex, and caudate nucleus (figure E). Western blot analysis of control and affected human and cat brain homogenates showed 3 PrP bands of 27-35 kDa. After digestion with proteinase K and deglycosylation, only samples from the affected patient and cat showed type-1 PrPres, with PrP glycoform ratios comparable to those observed in sporadic CJD1 (details available from author).
[Image]
Microscopic sections of patient and cat brains
A: Occipital cortex of the patient showing moderate spongiform degeneration and neuronal loss (haematoxylin and eosin) and B: punctate perineuronal pattern of PrP immunoreactivity; peroxidase immunohistochemistry with monoclonal antibody 3F4. C: cat parietal cortex showing mild spongiform degeneration (haematoxylin and eosin).D: vacuolated neurons (arrow, haematoxylin and eosin), E: peroxidase immunohistochemistry with antibody 3F4 shows punctate perineuronal deposition of PrP in temporal cortex.
This study shows a spatio-temporal association between human and feline prion diseases. The clinical features of the cat were different from previously reported cases of FSE which were characterised by gradual onset of behavioural changes preceding locomotor dysfunction and ataxia.5 Neuropathological changes were also at variance with the diffuse spongiosis and vacuolation of brainstem neurons, seen in FSE.5 The synaptic pattern of PrP deposition, similar in the cat and in the patient, was atypical for a BSE-related condition. Evidence of a new type of FSE was further provided by the detection of a type-1 PrPres, other than the BSE-associated type 4.2 Taken together, our data suggest that the same agent strain of sporadic CJD was involved in the patient and in his cat.
It is unknown whether these TSE occurred as the result of horizontal transmission in either direction, infection from an unknown common source, or the chance occurrence of two sporadic forms.
1 Parchi P, Castellani R, Capellari S, et al. Molecular basis of phenotypic variablity in sporadic Creutzfeldt-Jakob disease. Ann Neurol 1996; 39: 767-78 [PubMed].
2 Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF. Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature 1996; 383: 685-90 [PubMed].
3 Bruce ME, Will RG, Ironside JW, et al. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 1997; 389: 498-501 [PubMed].
4 Hill AF, Desbruslais M, Joiner S, et al. The same prion strain causes vCJD and BSE. Nature 1997; 389: 448-50 [PubMed].
5 Pearson GR, Wyatt JM, Henderson JP, Gruffydd-Jones TJ. Feline spongiform encephalopathy: a review. Vet Annual 1993; 33: 1-10.
------------------------------------------------------------------------ Sezione di Neurologie Clinica, Dipartimento di Scienze Neurologiche e della Visione, Università di Verona, Policlinico Borgo Roma, 37134 Verona, Italy (S Monaco; e mail rizzuto@Gorgorna.univr.it); and Istituto Zooprofilattico Sperimentale della Lombardia e dell' Emilia, Brescia
=======================================
Terry S. Singeltary Sr. wrote:
######## Bovine Spongiform Encephalopathy #########
Greetings list members,
ODD that some FELINE in Italy seem to have this same or maybe very similar phenotype of TSE;
In October 1998 the simultaneous occurrence of spongiform encephalopathy in a man and his pet cat was reported. The report from Italy noted that the cat did not display the same clinical features as FSE cases previously seen. Indeed, the presence of a new type of FSE was suggested. The man was diagnosed as having sporadic CJD, and neither case (man nor cat) appeared to be affected by a BSE-related condition.
http://www.defra.gov.uk/animalh/bse/bse-science/level-4-othertses.html
-------- Original Message --------
Subject: FDA BSE Update - Pet Food from Canadian Manufacturer & MAD DOG DATA
Date: Tue, 27 May 2003 08:07:58 -0500
From: "Terry S. Singeltary Sr."
To: Bovine Spongiform Encephalopathy
Statement
FOR IMMEDIATE RELEASE Statement May 26, 2003
Media Inquiries: 301-827-6242 Consumer Inquiries: 888-INFO-FDA
FDA BSE Update - Pet Food from Canadian Manufacturer
The Food and Drug Administration (FDA) has learned from the government of Canada that rendered material from a Canadian cow that last week tested positive for bovine spongiform encephalopathy (BSE, also known as mad cow disease ) may have been used to manufacture pet food, specifically dry dog food, some of which was reported to have been shipped to the United States. The Canadian government prevented the BSE positive cow from being processed for human food. Therefore, consumers can be assured that their food does not contain any remnants of the BSE positive cow.
It is also important to stress that there is no scientific evidence to date that dogs can contract BSE or any similar disease. In addition there is no evidence that dogs can transmit the disease to humans.
FDA notified the U.S. pet food firm, The Pet Pantry International, of Carson City, Nevada, when FDA learned that the pet food that the firm received may have included rendered material from the BSE positive cow. The manufacturer of the pet food is Champion Pet Food, Morinville, Alberta. Even though there is no known risk to dogs from eating this dog food, as a prudent measure to help assure that the U.S. stays BSE free The Pet Pantry International is asking its customers who may have purchased the suspect product to hold it for pickup by the distributor so that the dog food will not mistakenly be mixed into cattle or other feeds if any of the dog food is discarded or otherwise not used to feed dogs. The suspect dog food was produced by Champion Pet Food between February 4, 2003, and March 12, 2003.
The Pet Pantry products were packaged in 50 lb bags, distributed to franchises around the country, and sold by home delivery only. There was no retail distribution of the product. Consumers purchase Pet Pantry products by phone or email orders. The product is then delivered by the nearest franchisee directly to the consumer s home.
The product subject to this notification includes Maintenance Diet labeled with a use by date of 17FEB04 and Beef with Barley with a use by date of 05MAR04 . Consumers who have purchased dog food from The Pet Pantry since February of this year are asked to check their present supplies and see if any match the description of the product being removed. If so, consumers are asked to contact The Pet Pantry at 1-800-381-7387 for further information on how to return the product to The Pet Pantry for proper disposal. Consumers are asked not to destroy or discard the product themselves. The Pet Pantry will also use its sales records to contact consumers who purchased the affected product.
FDA is working closely with the Pet Pantry International to assure for proper disposal of the recovered product.
FDA will continue to provide updates on this case of BSE in Canada as additional information becomes available.
http://www.fda.gov/bbs/topics/NEWS/2003/NEW0910.html
It was thought likely that at least some, and probably all, of the cases in zoo animals were caused by the BSE agent. Strong support for this hypothesis came from the findings of Bruce and others (1994) ( Bruce, M.E., Chree, A., McConnell, I., Foster, J., Pearson, G. & Fraser, H. (1994)
Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and species barrier.
Philosophical Transactions of the Royal Society B 343, 405-411: J/PTRSL/343/405 ), who demonstrated that the pattern of variation in incubation period and lesion profile in six strains of mice inoculated with brain homogenates from an affected kudu and the nyala, was similar to that seen when this panel of mouse strains was inoculated with brain from cattle with BSE. The affected zoo bovids were all from herds that were exposed to feeds that were likely to have contained contaminated ruminant-derived protein and the zoo felids had been exposed, if only occasionally in some cases, to tissues from cattle unfit for human consumption.
snip...
http://collections.europarchive.org/tna/20080102174910/http://www.bseinquiry.gov.uk/files/ws/s324.pdf
cases have been reported in domestic cats), are characterised by long asymptomatic incubation periods followed by progressive symptoms and signs of degeneration of the brain, leading eventually to death.
http://www.bsereview.org.uk/download/draft_2.pdf
PET FOODS MAD CATS AND MAD DOGS BSE/TSEs
worse still, there is serious risk the media could get to hear of such a meeting...
snip...
Crushed heads (which inevitably involve brain and spinal cord material) are used to a limited extent but will also form one of the constituent raw materials of meat and bone meal, which is used extensively in pet food manufacturer...
http://collections.europarchive.org/tna/20080102163540/http://www.bseinquiry.gov.uk/files/yb/1989/03/17004001.pdf
2. The Parliamentary Secretary said that he was concerned about the possibility that countries in which BSE had not yet been detected could be exporting raw meat materials (in particular crushed heads) contaminated with the disease to the UK for use in petfood manufacture...
snip...
YOU explained that imported crushed heads were extensively used in the petfood industry...
http://collections.europarchive.org/tna/20080102154438/http://www.bseinquiry.gov.uk/files/yb/1989/04/14001001.pdf
In particular I do not believe one can say that the levels of the scrapie agent in pet food are so low that domestic animals are not exposed...
http://collections.europarchive.org/tna/20081105230259/http://www.bseinquiry.gov.uk/files/yb/1989/04/24003001.pdf
BSE IN PETFOOD
1. The Secretary asked on 19 April whether I was content with the advice in para 3 of the record of the meeting on 17 March with the Parliamentary Secretary (Mr Thompson). The simple answer is ''not entirely''.
2. On occasions, material obtained from slaughterhouses will be derived from sheep affected with scrapie or cattle that may be incubating BSE for use in petfood manufacture. Some of this material must be classified as high risk since it contains brain, spinal cord, spleen or lymphatic glands.
http://collections.europarchive.org/tna/20090505233052/http://www.bseinquiry.gov.uk/files/yb/1989/05/03007001.pdf
Meldrum's notes on pet foods and materials used
http://collections.europarchive.org/tna/20081105230323/http://www.bseinquiry.gov.uk/files/yb/1989/05/16001001.pdf
http://collections.europarchive.org/tna/20080102200123/http://www.bseinquiry.gov.uk/files/yb/1989/05/16002001.pdf
IN CONFIDENCE CJD TO CATS...
It should be noted that under experimental conditions cats succumb to an encephalopathy after intracerebral inoculation of material derived from patients affected with Creutzfeldt-Jakob Disease.
http://collections.europarchive.org/tna/20080103005226/http://www.bseinquiry.gov.uk/files/yb/1989/05/18002001.pdf
Confidential BSE and __________________
3. I have thought very hard about whether the Branch should carry out a similar exercise with meat and meat products for human foods. On balance I do NOT think we should undertake it, but a final decision has not been taken and you may wish to discuss this further. ...
http://web.archive.org/web/20030509205351/http://www.bseinquiry.gov.uk/files/yb/1989/05/22012001.pdf
full text ;
http://caninespongiformencephalopathy.blogspot.com/
http://betaamyloidcjd.blogspot.com/
Wednesday, February 24, 2010
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America 14th
ICID International Scientific Exchange Brochure -
http://transmissiblespongiformencephalopathy.blogspot.com/2010/02/transmissible-spongiform-encephalopathy.html
Transmissible Spongiform Encephalopathy
http://transmissiblespongiformencephalopathy.blogspot.com/
Monday, April 5, 2010
Update on Feed Enforcement Activities to Limit the Spread of BSE April 5, 2010
http://madcowfeed.blogspot.com/2010/04/update-on-feed-enforcement-activities.html
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