Saturday, February 16, 2013

What’s to like about the prion-like hypothesis for the spreading of aggregated α-synuclein in Parkinson disease?


transmission or seed ???



iatrogenic ???



what if ???







Prion 7:1, 92–97; January/February 2013; © 2013 Landes Bioscience 92 Prion V olume 7 Issue 1




What’s to like about the prion-like hypothesis for the spreading of aggregated α-synuclein in Parkinson disease?





Christopher J.R. Dunning,1,* Sonia George1 and Patrik Brundin1,2 1Neuronal Survival Unit; Wallenberg Neuroscience Center; Lund University; Lund, Sweden; 2Van Andel Research Institute; Center for Neurodegenerative Science; Grand Rapids, MI USA




Keywords: alpha-synuclein, prion-like, Parkinson disease, cell-to-cell transfer, protein misfolding




*Correspondence to: Christopher J.R. Dunning; Email: Christopher.Dunning@med.lu.se Submitted: 08/08/12; Revised: 01/17/13; Accepted: 01/28/13 http://dx.doi.org/10.4161/pri.23806




α-Synuclein is a key protein in Parkinson disease. Not only is it the major protein component of Lewy bodies, but it is implicated in several cellular processes that are disrupted in Parkinson disease. Misfolded α-synuclein has also been shown to spread from cell-to-cell and, in a prion-like fashion, trigger aggregation of α-synuclein in the recipient cell. In this minireview we explore the evidence that misfolded α-synuclein underlies the spread of pathology in Parkinson disease and discuss why it should be considered a prion-like protein.


Introduction




Parkinson disease (PD) is the second most prevalent neurodegenerative disease, and the most common synucleinopathy.




Synucleinopathies feature aggregated α-synuclein (α-syn) in intracellular inclusion bodies, which are termed Lewy bodies (LB) or Lewy neurites (LN) depending on their location. They are the classical neuropathological hallmark of PD and were first described by Friedrich Lewy a century ago.1 It is not clear why LB and LN form, or what impact these inclusions have on cell function. Proteomic analysis reveals they are comprised of greater than 100 different proteins,2 the major protein being α-syn. Since the discoveries that α-syn was the major protein component of Lewy aggregates,3 and that point mutations and genetic variation in the α-syn gene can cause rare forms of dominantly inherited PD, it has been a major focus for PD researchers. More recently, research on this little understood protein has taken an additional direction with the discovery that not only is α-syn the major protein component of LB and LN, but that intercellular exchange of the misfolded form might actually play a role in spreading α-syn pathology from cell-to-cell.




α-Syn is a 140 amino acid protein of predominantly presynaptic localization in neurons, although it is ubiquitously expressed.2,4 The protein is comprised of 3 domains: (1) an N-terminal lipid binding α-helix, (2) a non-amyloidβ component (NAC) domain and (3) an unstructured C-terminus. All three regions




α-Synuclein is a key protein in Parkinson disease. Not only is it the major protein component of Lewy bodies, but it is implicated in several cellular processes that are disrupted in Parkinson disease. Misfolded α-synuclein has also been shown to spread from cell-to-cell and, in a prion-like fashion, trigger aggregation of α-synuclein in the recipient cell. In this minireview we explore the evidence that misfolded α-synuclein underlies the spread of pathology in Parkinson disease and discuss why it should be considered a prion-like protein.




SNIP...




Why a Prion-Like Hypothesis Makes Sense




Why is α-syn described as prion-like and not prion? Certainly, as has been outlined here, misfolded α-syn could be responsible for the cellular transmission of PD pathology, although the underlying mechanisms remain elusive. On the other hand, the pathobiology of prion itself is relatively poorly understood. It is not known how it causes damage to its host cell, what form of prion oligomers are toxic, nor is its native function known. What we do know is that it is capable of cell-to-cell transmission and that it is a change in conformation from the normal cellular form (PrPC) to the toxic form (PrPSc) that causes toxicity. It is assumed that PrPSc acts as a seed for PrPC aggregation, a process that has been described as akin to that of crystal formation.80 While a seeding or nucleation process has also been described for α-syn, it has yet to be studied in the same level of detail as PrPSc and further work is needed to clarify whether nucleation does indeed occur. Perhaps the most striking difference between PrPSc and α-syn however is in its transmission. While biologically it seems that α-syn in its toxic amyloid form is transmissible from one cell to another,68,70 PrPSc is the only protein that has been shown to be transmissible at the organism level, i.e., from one individual to another. There is currently no evidence that misfolded α-syn can be transmitted from one individual to another. This lack of transmissibility might be coupled to the fact that α-syn has not been shown to be capable of self-replication. Thus with current knowledge, it is clear that α-syn is not a prion protein.




What the experiments highlighted above suggest though is that α-syn can act as a prion-like protein and the dynamic interplay that exists between misfolded α-syn and cellular dysfunction. Of course this interplay on its own could explain neurodegeneration in the PD brain.4 However, it does not fully explain the slow degeneration associated with the disease. There is little debate that PD is a disease that spreads. Pre-motor symptoms can appear decades before the on-set of motor-symptoms,81 and while not every PD patient exactly fits the staging scheme described by Braak,82 the degeneration observed in the majority of cases suggests a slow, progressive spread of neuropathology. The question remains, what causes this spread? And why are some neurons more vulnerable than others?




We know that transferred α-syn can recruit host α-syn, potentially depleting it from its site of normal function e.g., the synapse, which in turn can lead to a reduction in synaptic function, the consequences of which were discussed briefly above. If the transferred protein is misfolded, and consequently causes more protein to misfold, then it is possible α-syn acquires a “novel” function, that of a protein complex that binds and disrupts membranes, again causing stress to the cell. We also know that α-syn levels increase with age. As with all proteins, sometimes it misfolds. As our cells contain more and more α-syn, the proportion of misfolded α-syn will increase, causing greater burden to the cellular machinery tasked with dealing with misfolded protein. While LBs or LNs can appear in most, if not all, cells of the brain, certain cells appear more vulnerable to degeneration than others.83 The reason for this is likely to lie in the cells ability to handle toxic protein i.e., misfolded α-syn. A cell with a high energy requirement will be less able to cope with an influx of toxic protein, likewise a cell which is rich in ROS is likely to provide the right environment for further α-syn aggregation and subsequent spread of pathology. The spread of pathology is also a very slow process, suggesting that the cell can cope for a certain period of time and only when a threshold is reached does sufficient degeneration occur.




Is α-Synuclein a Prion-Like Protein?




There are three factors that have been described for α-syn that are common to other prion-like proteins. (1) α-Syn has different conformations. Under physiological conditions it is predominantly unstructured or α-helical (possibly organized in a tetramer) in structure. The pathological form of α-syn consists of oligomers and fibrils rich in β-sheets. (2) α-Syn transfers from cell-to-cell. Whether or not it transfers to a higher degree than other proteins is unknown, but it is clear that aggregated α-syn can transfer between cells. (3) Aggregated α-syn has been shown to propagate in vivo. Direct catalysis of misfolding of endogenous α-syn has not been observed in these instances, but a time dependent increase in aggregation is clear.




The trigger that leads to misfolding and aggregation of α-syn remains unknown. In a number of rare cases, mutations in the α-syn gene alone may be enough, but in the majority of cases a number of factors are likely to contribute. What is becoming clear however, whatever the trigger, misfolded α-syn is the likely bullet, spreading synuclein pathology throughout the brain.


What’s to like about the prion-like hypothesis for the spreading of aggregated α-synuclein in Parkinson disease?




Christopher J.R. Dunning,1,* Sonia George1 and Patrik Brundin1,2 1Neuronal Survival Unit; Wallenberg Neuroscience Center; Lund University; Lund, Sweden; 2Van Andel Research Institute; Center for Neurodegenerative Science; Grand Rapids, MI USA




Keywords: alpha-synuclein, prion-like, Parkinson disease, cell-to-cell transfer, protein misfolding



















Sunday, February 10, 2013



Parkinson's Disease and Alpha Synuclein: Is Parkinson's Disease a Prion-Like Disorder?












Friday, February 15, 2013



Scottish TSE Network November Symposium Announcement Event: 12 November 2012 Title: Is Alzheimer’s Disease a transmissible disease? SUMMARY










Thursday, February 14, 2013



The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and TSE prion disease











TSS

Friday, February 15, 2013

Scottish TSE Network November Symposium Announcement Event: 12 November 2012 Title: Is Alzheimer’s Disease a transmissible disease? SUMMARY

Scottish TSE Network November Symposium Announcement Event: 12 November 2012 Title: Is Alzheimer’s Disease a transmissible disease? SUMMARY




Cell to cell spread of misfolded protein




A meeting was held on the 12th November hosted by the Scottish Transmissible Spongiform Encephalopathy Network (STN) at the Roslin Institute, University of Edinburgh with the aim of examining whether Alzheimer's disease should be classed as a “transmissible disease”? Speakers included international experts in prion and Alzheimer's diseases examining the evidence from studies in the human population and in animal models. The presentations reviewed the current position and the final discussion drew some important conclusions.




It is well known that in prion diseases an abnormal misfolded protein (PrPSc) derived from a normal host protein (PrPC) accumulates and spreads through the brain along defined neuroanatomical pathways. Prion diseases affect both animals (scrapie in sheep, BSE in cattle, chronic wasting disease in deer) and humans (Creutzfeldt - Jakob Disease (CJD)). Transmission between individuals in the natural state has been observed for some prion diseases, for example in sheep and deer. Many, although not all, prion diseases in animals can be experimentally transmitted from animal to animal, and one has transmitted from animal to human,BSE. CJD can also be transmitted to experimental animals. However, transmission of CJD between humans only occurs very rarely and in exceptional circumstances such as the transfer of tissue from an individual with CJD to another by a surgical procedure or via certain medical treatments. Transmission between individuals and spread from cell to cell within an individual, have both been termed “prion transmission”.




It has been shown in neuropathological studies of brains from patients with Alzheimer’s disease that the pathology also spreads in a predictable way through the brain. This spread of pathology in the grey matter of the brain involves the formation of amyloid plaques, comprised of A, outside nerve cells, and neurofibrillary tangles inside nerve cells. Mice carrying human genes that lead to the deposition of the A peptide in the brain have been used to study aspects of Alzheimer’s disease pathology. Experimental studies show that injection of A plaque material, isolated from a human Alzheimer’s disease brain, or another mouse with A plaques can accelerate the deposition of A in the brain and its deposition along neuronal pathways. This predictable spread from cell to cell has been referred to as “prion-like transmission” and has now been demonstrated not only in mouse models with the A protein, but also in other models of neurodegenerative disease that involve the misfolding of proteins. It was suggested by several of the speakers that the injected misfolded peptide or protein acts as a “seed” for further deposition of misfolded protein akin to the growth of a crystal. It is likely that there are considerable parallels between prion diseases and Alzheimer’s disease in the molecular and cellular events leading to cell to cell transmission.




There is no evidence to date from analysis of patient populations that transmission of Alzheimer’s disease between individuals has occurred. It was concluded that human to human transmission of any protein misfolding disease requires a set of very unusual circumstances to occur, as has been documented in the prion diseases. The evidence from human and animal studies does not support the idea that Alzheimer's disease is transmissible between individuals. The term “prion-like transmission” has been unhelpful in the context of Alzheimer’s disease and other protein misfolding diseases as it does not distinguish between spread between cells and transmission between individuals. The meeting concluded that the term “prion-like cell to cell spread” should be used to convey a clear message. The robust experimental models in prion disease provide an opportunity to understand the cellular and molecular mechanisms of cell to cell spread and identify therapeutic targets to delay disease progression for both prion and Alzheimer’s disease.




Professor Jean Manson, The Roslin Institute, University of Edinburgh and R(D)SVS Easter Bush Professor Hugh Perry, University of Southampton




END...TSS







UPDATE JUNE 28, 2012




Scottish TSE Network November Symposium Announcement Event: 12 November 2012




Chair: Prof Hugh Perry, University of Southampton, Southampton UK




Location: The Roslin Institute Building Auditorium




If you would like to book a place at this event, please let Gila Holliman know.




Cost: £125.




Title: Is Alzheimer’s Disease a transmissible disease?




Speakers:




Session 1:


Prof Bob Will, National CJD Surveillance Unit, Edinburgh UK


Prof James Ironside, National CJD Surveillance Unit, Edinburgh UK


Prof Lary Walker, Emory School of Medicine, Atlanta USA




Session 2:


Prof Mathias Jucker, Hertie Institute for Clinical Brain Research, Stuttgart Germany


Prof William Van Nostrand, Stony Brook University, Stony Brook USA


Dr Claudio Soto, University of Texas Medical School, Houston USA




Session 3:


Dr Fabrizio Tagliavini, Instituto Neurologico Carlo Besta, Milan Italy


Prof Pedro Piccardo, Food and Drug Administration, Washington DC USA


Dr Bruce Chesebro, National Institutes of Health, Missoula USA













Transmission of Prions and Alzheimer’s disease Abeta Amyloid




Claudio Soto, PhD




Mitchell Center for Alzheimer’s disease and Related Brain Disorders, Dept of Neurology




University of Texas Medical School at Houston











Tuesday, October 4, 2011




Molecular Psychiatry




advance online publication 4 October 2011; doi: 10.1038/mp.2011.120




De novo induction of amyloid-ß deposition in vivo




Our results suggest that some of the typical brain abnormalities associated with AD can be induced by a prion-like mechanism of disease transmission through propagation of protein misfolding. These findings may have broad implications for understanding the molecular mechanisms responsible for the initiation of AD, and may contribute to the development of new strategies for disease prevention and intervention. Keywords: amyloid; prion; protein misfolding; disease transmission








see more here ;















Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?




Background




Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease have both been around a long time, and was discovered in or around the same time frame, early 1900’s. Both diseases are incurable and debilitating brain disease, that are in the end, 100% fatal, with the incubation/clinical period of the Alzheimer’s disease being longer (most of the time) than the TSE prion disease. Symptoms are very similar, and pathology is very similar.




Methods




Through years of research, as a layperson, of peer review journals, transmission studies, and observations of loved ones and friends that have died from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant Creutzfelt Jakob Disease CJD.




Results




I propose that Alzheimer’s is a TSE disease of low dose, slow, and long incubation disease, and that Alzheimer’s is Transmissible, and is a threat to the public via the many Iatrogenic routes and sources. It was said long ago that the only thing that disputes this, is Alzheimer’s disease transmissibility, or the lack of. The likelihood of many victims of Alzheimer’s disease from the many different Iatrogenic routes and modes of transmission as with the TSE prion disease.




Conclusions




There should be a Global Congressional Science round table event set up immediately to address these concerns from the many potential routes and sources of the TSE prion disease, including Alzheimer’s disease, and a emergency global doctrine put into effect to help combat the spread of Alzheimer’s disease via the medical, surgical, dental, tissue, and blood arena’s. All human and animal TSE prion disease, including Alzheimer’s should be made reportable in every state, and Internationally, WITH NO age restrictions. Until a proven method of decontamination and autoclaving is proven, and put forth in use universally, in all hospitals and medical, surgical arena’s, or the TSE prion agent will continue to spread. IF we wait until science and corporate politicians wait until politics lets science _prove_ this once and for all, and set forth regulations there from, we will all be exposed to the TSE Prion agents, if that has not happened already.




end...tss







SEE FULL TEXT AND SOURCE REFERENCES ;






Wednesday, May 16, 2012




Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?




Proposal ID: 29403











Wednesday, September 21, 2011




PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS)











Wednesday, February 6, 2013




Penn study confirms no transmission of Alzheimer's proteins between humans ?




ONLINE FIRST




ORIGINAL CONTRIBUTION




Evaluation of Potential Infectivity of Alzheimer and Parkinson Disease Proteins in Recipients of Cadaver-Derived Human Growth Hormone




David J. Irwin, MD; Joseph Y. Abrams, MPH; Lawrence B. Schonberger, MD, MPH; Ellen Werber Leschek, MD; James L. Mills, MD, MS; Virginia M.-Y. Lee, PhD, MBA; John Q. Trojanowski, MD, PhD




Importance: Growing evidence of cell-to-cell transmission of neurodegenerative disease (ND)–associated proteins (NDAPs) (ie, tau, A , and -synuclein) suggests possible similarities to the infectious prion protein (PrPsc) in spongiform encephalopathies. There are limited data on the potential human-to-human transmission of NDAPs associated with Alzheimer disease (AD) and other non- PrPsc ND.




Objective: To examine evidence for human-to-human transmission of AD, Parkinson disease (PD), and related NDAPs in cadaveric human growth hormone (chGH) recipients.




Design: We conducted a detailed immunohistochemical analysis of pathological NDAPs other than PrPsc in human pituitary glands. We also searched for ND in recipients of pituitary-derived c-hGH by reviewing the National Hormone and Pituitary Program (NHPP) cohort database and medical literature.




Setting: University-based academic center and agencies of the US Department of Health and Human Services. Participants: Thirty-four routine autopsy subjects (10 non-ND controls and 24 patients with ND) and a US cohort of c-hGH recipients in the NHPP. Main Outcome Measures: Detectable NDAPs in human pituitary sections and death certificate reports of non- PrPsc ND in the NHPP database.




Results: Wefound mild amounts of pathological tau, A , and -synuclein deposits in the adeno/neurohypophysis of patients with ND and control patients. No cases of AD or PD were identified, and 3 deaths attributed to amyotrophic lateral sclerosis (ALS) were found among USNHPP c-hGH recipients, including 2 of the 796 decedents in the originally confirmed NHPP c-hGH cohort database.




Conclusions and Relevance: Despite the likely frequent exposure of c-hGH recipients to NDAPs, and their markedly elevated risk of PrPsc-related disease, this population of NHPP c-hGH recipients does not appear to be at increased risk of AD or PD. We discovered 3 ALS cases of unclear significance among US c-hGH recipients despite the absence of pathological deposits of ALS-associated proteins (TDP-43, FUS, and ubiquilin) in human pituitary glands. In this unique in vivo model of human-to-human transmission, we found no evidence to support concerns that NDAPs underlyingADand PD transmit disease in humans despite evidence of their cell-to-cell transmission in model systems of these disorders. Further monitoring is required to confirm these conclusions.




JAMA Neurol. Published online February 4, 2013. doi:10.1001/jamaneurol.2013.1933





SNIP...





COMMENT




Our findings herein indicate that pathological species of tau, A , and -synuclein are found in the adeno/ neurohypophysis of normal individuals and those with ND, but, this notwithstanding, these NDAPs are unlikely to propagate between individuals as a diseasecausing infectious agent based on our review of the NHPP database for the following reasons.




First, it is highly likely that c-hGH recipients were exposed to the pathogenic proteins (ie, tau, A , and -synuclein) of AD, PD, and FTLD-tau during the frequent administration of c-hGH that patients received over periods of several years. This assumption is based on the fact that low levels of pathological deposits of these NDAPs were present in both affected and unaffected subjects in our immunohistochemical analysis. Indeed, a similar burden of PrPsc inclusions has been demonstrated in the neurohypophysis of sporadic CJD cases, thereby establishing pituitary gland extracts as the likely source of PrPsc for c-hGH recipients.28 Compared with CJD with an incidence of about 1 case per million, the incidence of AD is at least 3 orders of magnitude higher and the inci-dence of PD at least 2 orders of magnitude higher.29 Thus, provided the pathogenic species of the NDAPs linked to AD, FTLD-tau, and PD as well as PrPsc were similarly affected by the c-hGH purification process, c-hGH recipients would most likely have had a much higher probability of exposure to pathological tau, A , and -synuclein than to PrPsc. In addition, our observations of abnormal deposits of NDAPs in aged control pituitary tissue further increase the likelihood of potential exposure to these proteins.




Second, although more than 200 cases of iatrogenic CJD have been identified to date among the estimated 30 000 c-hGH recipients treated between 1959 and 1985 worldwide30 (7700 in the United States, 1880 in France, and 1800 in the United Kingdom alone23), we found no reports of AD, FTLD, or PD, suggesting that these diseases may not be transmissible between humans.




Several caveats should be noted regarding the interpretation of these findings. First, it is currently unclear which species ofNDAPs(monomers, oligomers, or fibrillar forms) is responsible for transmission seen in published models of disease, although the reports by Luk et al2,3 used preformed -synuclein fibrils to transmit lethal Lewy body disease in an animal model. We demonstrate varying degrees of both amyloid-like and diffuse deposits for A , tau, and -synuclein in the neurohypophysis (Figure 1 and Figure 2). Despite the relative stability of PrPsc, it is still probable that most forms of these non-PrPscNDAPsobserved herein could also survive the relatively crude sequential extraction process used to purify c-hGH prior to 1977 in the United States,31 because the pathological species of NDAPs in AD and related proteinopathies are known to remain insoluble in harsher detergents used in experimental sequential extraction techniques.32,33




Our retrospective analysis is limited to reports in the literature and interrogation of a death certificate database that may not be comprehensive enough to detect all clinically manifest NDs. Indeed, neurologic diseases (ie, neoplasms, head trauma, and radiation necrosis) that occur in some c-hGH recipients may be difficult to distinguish from an emerging ND. However, the NHPP database did enable recognition of an increase in CJD in the US cohort of NHPP c-hGH recipients.




Another uncertainty is the potential incubation period for transmitted NDAPs. The reported mean incubation time for prion disease from midpoint of treatment in c-hGH recipients worldwide was 17 years but ranged from 5 to as long as 42 years.23 Endocrine failure or the underlying etiology of hormone deficiency contributed substantially to the young mean age at death of the patients in our cohort (27.2 years) (eTable 2).34 Despite this, more than half the deceased patients survived 15 years or more after the midpoint of c-hGH treatment, and 19% survived 25 years or more (eTable 2). Additionally, the large number of living patients (about 4600 of the cohort) also have not died of an ND after a long follow-up period of 25 years or more from the initial treatment (eTable 2).




The time required for the underlying neuropathology to cause clinical disease in non-PrPsc ND is not clear, but most likely it varies widely among different individuals and commonly spans several decades. There is evidence of neuropathological changes long before the onset of clinical disease. Early preneurofibrillary tangle pathology has been found in asymptomatic patients as young as the first decade of life.35 Furthermore, biomarker studies of AD suggest amyloidosis may be evident decades before clinical symptoms in AD.36,37 Indeed, new criteria to identify asymptomatic “preclinical” AD highlight the importance of AD neuropathological change as an abnormal prodrome to clinical AD.38 As such, it is possible that susceptible c-hGH patients could be in an early asymptomatic phase of transmitted ND that may not have become clinically manifested yet and thus not detected by our study. The lack of autopsy data for the NHPP cohort limits our ability to examine for evidence of a potential subclinical NDAP transmission and thus provide a more definitive conclusion on the subclinical human-to-human transmission of NDAPs; however, we found no evidence to support clinical transmission of AD or PD in this unique cohort after a relatively long incubation period (as compared with our experience with CJD). Continued follow-up of recipients of c-hGH, with reviews of the clinical and autopsy records of those who may die in the future with anNDlisted as a cause of death, will be important to confirm these findings.




The discovery of 2 deaths attributed to ALS among the initially confirmed cohort of NHPP c-hGH recipients and 1 additional case identified in the literature, especially at such young ages, is disquieting. However, the identification of ALS cases among c-hGH recipients does not definitively indicate transmission of pathogenic TDP- 43, ubiquilin, or FUS since we found no evidence of these proteins in the adeno/neurohypophysis of any of the cases studied herein. Notably, unlike tau, A , and -synuclein pathology, no abnormal TDP-43 deposits occur in the olfactory epithelium as well.26 These data suggest it is very unlikely c-hGH recipients were exposed to ALSassociated pathogenic proteins (ie, TDP-43, FUS, and ubiquilin). Furthermore, autopsy was not performed in 1 case and the others lacked state-of-the-art techniques for modern diagnosis; thus, the molecular etiology of the clinical syndrome in these cases remains uncertain. Indeed, 1 case was described to have degeneration of sensory tracts,27 which is atypical for ALS. Although the earlier- mentioned data suggest infectivity to be an unlikely etiology, surveillance of the c-hGH cohort for ALS and related NDs is necessary to monitor the occurrence of additional cases.




In our follow-up of the unusually young ALS casepatient identified in our literature review,27 we learned that no transmission of ALS per se occurred in a capuchin monkey that in September 1986 had received an intracerebral inoculation of 0.1 mL of a 20% suspension of this patient’s frozen cervical cord tissue. The inoculated monkey died in August 1997 without having developed signs of a neurological disease; an autopsy report, however, was unavailable (P. Brown, MD, and D. M. Asher, MD, oral and written communication, June 18 and 25, 2012). In addition, since the early 1970s, investigators at the National Institutes of Health conducted primate transmission studies with tissues from 58 other cases of ALS, 105 cases of AD, and 24 cases of PD with dementia; in none of these studies did the inoculated pri- mates develop lower motor neuron signs, behavioral changes, or a movement disorder consistent with a non- PrPsc ND, nor did neuropathologists find postmortem evidence for the transmission of these diseases39 (P. Brown, MD, and D. M. Asher, MD, oral and written communication, June 18 and 25, 2012). In contrast, there were at least 300 cases of experimentally transmitted prion diseases during this same period.39 Despite this substantial negative body of evidence for non-PrPsc ND transmission in nonhuman primates, 2 studies in the early 1990s reported that subclinical AD-like plaques were induced in marmosets following central nervous system inoculation with human brain lysates (0.3 mL of 10% saline suspensions).40,41 The majority of human brain lysates shown to induce A pathology in these studies were derived from CJD cases and not AD and there was also no evidence of transmission of clinical disease or tau pathology in any of these inoculated primates.




To our knowledge, only 1 other group of human subjects can provide some additional insights into the transmissibility of NDAPs and that is those patients with PD who received striatal fetal mesencephalic grafts as experimental therapy. Neurons within these grafts showed evidence of PD-like -synuclein Lewy body pathology, but the number of patients whose grafts showed this pathology was small and only rare grafted neurons developed -synuclein Lewy body pathology at or beyond 10 years postgrafting.42-45 However, while this -synuclein pathology could reflect the transmission of pathological -synuclein from the host striatum to the grafted neurons, other explanations are possible, such as the effects of the hosts’ PD neurodegenerative condition on the grafts aside from the -synuclein pathology.12,46




In summary, despite the limitations of this study discussed earlier, to our knowledge, we provide the most compelling human in vivo evidence currently available to suggest that while there are some similarities between the cell-to-cell spread of PrPsc and non-PrPsc NDAPs in experimental models there is currently no documentation that AD, FTLD-tau, or PD-associated proteins (ie, tau, A , or -synuclein) transmit disease in human or nonhuman primates like PrPsc. Prospective monitoring of all c-hGH recipients for CJD and non-PrPsc NDs should be continued.




Accepted for Publication: November 27, 2012. Published Online: February 4, 2013. doi:10.1001 /jamaneurol.2013.1933 Author Affiliations: Center







Wednesday, February 6, 2013



Penn study confirms no transmission of Alzheimer's proteins between humans ?











Sunday, February 10, 2013



Parkinson's Disease and Alpha Synuclein: Is Parkinson's Disease a Prion-Like Disorder?




















Thursday, February 14, 2013



The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and TSE prion disease










TSS

Sunday, February 10, 2013

Parkinson's Disease and Alpha Synuclein: Is Parkinson's Disease a Prion-Like Disorder?

Review






Parkinson's Disease and Alpha Synuclein: Is Parkinson's Disease a Prion-Like Disorder?





C. Warren Olanow MD1,*, Patrik Brundin MD, PhD2,3





Article first published online: 6 FEB 2013





DOI: 10.1002/mds.25373





Copyright © 2013 Movement Disorder Society







Additional Information(Hide All) How to CiteAuthor InformationPublication History How to Cite Olanow, C. W. and Brundin, P. (2013), Parkinson's Disease and Alpha Synuclein: Is Parkinson's Disease a Prion-Like Disorder?. Mov. Disord., 28: 31–40. doi: 10.1002/mds.25373






Author Information 1 Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, USA 2 Van Andel Research Institute, Center for Neurodegenerative Science, Grand Rapids, Michigan, USA 3 Neuronal Survival Unit, BMC B11, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden *Correspondence to: Dr. C. Warren Olanow, Department of Neurology, Mount Sinai School of Medicine, Annenberg 20–92, One Gustave L. Levy Place, Box 1137, New York, NY 10029; warren.olanow@mssm.edu






Relevant conflicts of interest/financial disclosures: Nothing to report.






Full financial disclosures and author roles may be found in the online version of this article.






Publication History Issue published online: 6 FEB 2013 Article first published online: 6 FEB 2013 Manuscript Accepted: 2 JAN 2013 Manuscript Received: 26 DEC 2012






Keywords:misfolded α-synuclein;β-sheet formation;Lewy-like pathology;prions;toxic oligomers




ABSTRACT





Altered protein handling is thought to play a key role in the etiopathogenesis of Parkinson's disease (PD), as the disorder is characterized neuropathologically by the accumulation of intraneuronal protein aggregates (Lewy bodies and Lewy neurites). Attention has particularly focused on the α-synuclein protein, as it is the principal component of Lewy pathology. Moreover, point mutations in the α-synuclein gene cause rare familial forms of PD. Importantly, duplication/triplication of the wild type α-synuclein gene also cause a form of PD, indicating that increased levels of the normal α-synuclein protein is sufficient to cause the disease. Further, single nucleotide polymorphisms in the α-synuclein gene are associated with an increased risk of developing sporadic PD. Recent evidence now suggests the possibility that α-synuclein is a prion-like protein and that PD is a prion-like disease. Within cells, α-synuclein normally adopts an α-helical conformation. However, under certain circumstances, the protein can undergo a profound conformational transition to a β-sheet–rich structure that polymerizes to form toxic oligomers and amyloid plaques. Recent autopsy studies of patients with advanced PD who received transplantation of fetal nigral mesencephalic cells more than a decade earlier demonstrated that typical Lewy pathology had developed within grafted neurons. This suggests that α-synuclein in an aberrantly folded, β-sheet–rich form had migrated from affected to unaffected neurons. Laboratory studies confirm that α-synuclein can transfer from affected to unaffected nerve cells, where it appears that the misfolded protein can act as a template to promote misfolding of host α-synuclein. This leads to the formation of larger aggregates, neuronal dysfunction, and neurodegeneration. Indeed, recent reports demonstrate that a single intracerebral inoculation of misfolded α-synuclein can induce Lewy-like pathology in cells that can spread from affected to unaffected regions and can induce neurodegeneration with motor disturbances in both transgenic and normal mice. Further, inoculates derived from the brains of elderly α-synuclein–overexpressing transgenic mice have now been shown to accelerate the disease process when injected into the brains of young transgenic animals. Collectively, these findings support the hypothesis that α-synuclein is a prion-like protein that can adopt a self-propagating conformation that causes neurodegeneration. We propose that this mechanism plays an important role in the development of PD and provides novel targets for candidate neuroprotective therapies. © 2013 Movement Disorder Society














Sunday, December 9, 2012


Prions, prionoids and pathogenic proteins in Alzheimer disease


Mini-Review











Wednesday, September 21, 2011




PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic





Lateral Sclerosis (ALS)




Researchers’ Discovery May Revolutionize Treatment of ALS





PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS)






September 20, 2011 (Vancouver, BC) - A team of researchers from the University of British Columbia and the Vancouver Coastal Health Research Institute have found a key link between prions and the neurodegenerative disease ALS (Amyotrophic Lateral Sclerosis), also known as Lou Gehrig’s disease. The discovery is significant as it opens the door to novel approaches to the treatment of ALS.





A pivotal paper published by the team this week in the Proceedings of the National Academy of Sciences (PNAS), demonstrates that the SOD1 protein (superoxide dismutase 1), which has been shown to be implicated in the ALS disease process, exhibits prion-like properties. The researchers found that SOD1 participates in a process called template-directed misfolding. This term refers to the coercion of one protein by another protein to change shape and accumulate in large complexes in a fashion similar to the process underlying prion diseases.





These findings provide a molecular explanation for the progressive spread of ALS through the nervous system, and highlight the central role of the propagation of misfolded proteins in the pathogenesis of neurodegenerative diseases, including ALS, Alzheimer’s and Parkinson’s.





“Our work has identified a specific molecular target, which when manipulated halts the conversion of the SOD1 protein to a misfolded, disease-causing form,” says Dr. Neil Cashman, Scientific Director of PrioNet Canada, Canada Research Chair in Neurodegeneration and Protein Misfolding at UBC, and academic director of the Vancouver Coastal Health ALS Centre. “This discovery is a first-step toward the development of targeted treatments that may stop progression of ALS.”





ALS is a progressive neuromuscular disease in which nerve cells die, resulting in paralysis and death. Approximately 2,500 to 3,000 Canadians currently live with this fatal disease, for which there is no effective treatment yet.





“For many years, ALS has remained a complex puzzle and we have found a key piece to help guide the research community to solutions,” says Dr. Leslie Grad, a co-first author of the project and current Manager of Scientific Programs at PrioNet Canada. “PrioNet is further exploring this discovery through newly-funded research projects.”





The work was completed by Dr. Neil Cashman’s lab at the Brain Research Centre based at the University of British Columbia and the Vancouver Coastal Health Research Institute, in collaboration with researchers at the University of Alberta. The research was supported by PrioNet Canada and in part by Amorfix Life Sciences and the Canadian Institutes of Health Research.





PrioNet Canada, based in Vancouver, has achieved international attention for scientific discoveries and risk management strategies directed at controlling prion diseases, and is now directing capacity into therapeutic solutions for prion-like diseases of aging, such as Alzheimer’s, Parkinson’s and ALS.





About: One of Canada’s Networks of Centres of Excellence, PrioNet Canada (www.prionetcanada.ca) is developing strategies to help solve the food, health safety, and socioeconomic problems associated with prion diseases. The network brings together scientists, industry, and public sector partners through its multidisciplinary research projects, training programs, events, and commercialization activities. PrioNet is hosted by the University of British Columbia and the Vancouver Coastal Health Research Institute in Vancouver.





The University of British Columbia (UBC) is one of North America’s largest public research and teaching institutions, and one of only two Canadian institutions consistently ranked among the world’s 40 best universities. UBC is a place that inspires bold, new ways of thinking that have helped make it a national leader in areas as diverse as community service learning, sustainability and research commercialization. UBC offers more than 50,000 students a range of innovative programs and attracts $550 million per year in research funding from government, non-profit organizations and industry through 7,000 grants.





Vancouver Coastal Health Research Institute (VCHRI) (www.vchri.ca) is the research body of Vancouver Coastal Health Authority, which includes BC’s largest academic and teaching health sciences centres: VGH, UBC Hospital, and GF Strong Rehabilitation Centre. In academic partnership with the University of British Columbia, VCHRI brings innovation and discovery to patient care, advancing healthier lives in healthy communities across British Columbia, Canada, and beyond.





The Brain Research Centre comprises more than 200 investigators with multidisciplinary expertise in neuroscience research ranging from the test tube, to the bedside, to industrial spin-offs. The centre is a partnership of UBC and Vancouver Coastal Health Research Institute. For more information, visit www.brain.ubc.ca.






- 30 -







Media information or to set up interviews: Gail Bergman, Gail Bergman PR Tel: (905) 886-1340 or (905) 886-3345 E-mail: info@gailbergmanpr.com








Backgrounder - ALS as a "prion-like" disease







Amyotrophic lateral sclerosis (ALS): Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig ’s disease in the United States and motor neurone disease (MND) in Europe, is a fatal neurodegenerative disease caused by deterioration of motor neurons in the brain and spinal cord. Individuals living with the disease experience progressive paralysis, as well as difficulty breathing or swallowing. At this time, no cure or effective treatment exists.





According to the ALS Society of Canada: • ALS is the most common cause of neurological death • Every day two or three Canadians die of ALS • Eighty per cent of people with ALS die within two to five years of diagnosis; ten per cent of those affected may live for 10 years or longer • Approximately 2,500 - 3,000 Canadians currently live with this fatal disease • The World Health Organization predicts that neurodegenerative diseases will surpass cancer as the second leading cause of death in Canada by 2040





Background: Recent research highlights links between the biological mechanisms of common neurological disorders, such as ALS, Alzheimer’s and Parkinson’s disease with prion disease. While each of these diseases manifests itself in a different way, the hallmark of each is a progressive accumulation of misfolded protein aggregates in the central nervous system.





Correctly-folded proteins adopt one particular structure in order to carry out their intended function. A protein’s failure to adopt this correct structure is what threatens the health of cells. Prions are “misfolded” proteins -- the infectious, aggregating agents in diseases such as Creutzfeldt-Jakob disease (CJD) in humans, chronic wasting disease (CWD) in deer and elk and bovine spongiform encephalopathy (BSE), also known as “mad cow” disease in cattle. In ALS, Alzheimer’s and Parkinson’s, the misfolded proteins are SOD1, amyloid-ß, and a-synuclein, respectively.





Key Finding: “Intermolecular transmission of SOD-1 misfolding in living cells” - Published in the Proceedings of the National Academy of Sciences (PNAS), September 2011 • The paper shows that superoxide dismutase 1 (SOD1) participates in template-directed misfolding, in other words, the coercion of one protein by another protein to change shape and aggregate such as prion diseases do. • The results will be significant to the ALS field because it connects prion mechanisms behind the biological progression of ALS, and provides a molecular explanation for the linear and temporal spread of ALS through the nervous system. • Furthermore, the research has identified a specific molecular target, which when manipulated, halts the conversion of SOD1 to a misfolded, disease-causing form. This is a first-step towards the development of targeted treatments that may stop ALS, which PrioNet is further exploiting through newly-funded research. • This research was supported by PrioNet Canada and in part by Amorfix Life Sciences and the Canadian Institutes of Health Research.





Other Research: Studies showing how “seed” misfolded protein induce aggregation of other protein, which provide evidence for prion-like spread: • Lary Walker’s group at Emory University in Atlanta, in collaboration with Matthias Jucker and others at the Universities of Tübingen in Germany and Basel in Switzerland, discovered that aggregates of amyloid-ß protein from the brain of people with Alzheimer’s disease could be transmitted to the brain of healthy mice. • Another study by Patrik Brundin’s group in Sweden demonstrated that healthy tissue surgically implanted into the brain of people with Parkinson’s disease acquired the aggregates of a-synuclein protein characteristic of the disease. • Eliezer Masliah of the University of California San Diego and others discovered that aggregates of a-synuclein can travel from cell to cell, forming the aggregates in human neurons that are characteristic of Parkinson’s disease and certain types of dementia. • Anne Bertolotti from the University of Cambridge discovered that neuronal cells spontaneously and efficiently take up misfolded mutant SOD1 from their environment. The internalized mutant SOD1 triggers a change in shape of the normally soluble mutant SOD1 protein, which causes its aggregation, and is then transferred to neighbouring cells in a prion-like fashion.





Last Updated: 9/20/2011 3:19:45 PM





posted: 9/20/2011













snip...see full test ;














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.







Friday, September 3, 2010.


Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE.











Wednesday, September 21, 2011.


PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS).











Wednesday, January 5, 2011.


... ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions.


David W. Colby1,* and Stanley B. Prusiner1,2














Saturday, January 22, 2011


Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there of, a review 2011











Friday, September 3, 2010


Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE











Sunday, August 8, 2010


The Transcellular Spread of Cytosolic Amyloids, Prions, and Prionoids











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







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











see full text and more science on this topic here ;











13





Simultaneous Onset of Alzheimer's Disease in a Husband and Wife in Their Mid Fifties: What do We Really Know?





Jonathan Heath1, Lindsay Goicochea2, Mark Smith3, Rudy Castellani4. 1Department of Pathology, University of Maryland; 2University; 3Case Western Reserve University; 4University of Maryland, Baltimore, Maryland





Whereas the genetic factors influencing the development and expression of Alzheimer's disease are well characterized, environmental factors are currently thought to play a marginal role. Such factors as prior closed head injury, post-menopausal estrogen deficiency, aluminum exposure, smoking, diabetes, atherosclerotic cardiovascular disease, and diet, among others, confer only a modest increased risk if any, and are only tangentially considered in the major pathogenic cascades that are presently hypothesized. We present the simultaneous onset of Alzheimer's disease in a husband and wife, with both subjects experiencing cognitive dysfunction within the same month. Both subjects were in their mid-fifties at the time of presentation, both subjects showed progressively neurological decline with prominent memory loss, both subjects experienced myoclonus late in their disease course prompting referral to the National Prion Disease Pathology Surveillance Center, and both subjects expired 12 years after onset, within two months of each other. Review of the family pedigree revealed no family history of dementia or other neurologic illnesses in multiple first degree relatives. The only historical finding of note was that both subjects had moved out of their home briefly while it was being remodeled, and both became symptomatic shortly after moving back in. At autopsy, the subjects had classic advanced Alzheimer's disease, with Braak stage VI pathology that was otherwise identiical in quantity and distribution of amyloid-beta, cerebral amyloid angiopathy, and neurofibrillary degeneration. While no specific toxin or other environmental cause was discerned, these two cases raise the issue of epigenetic factors in Alzheimer's disease that may be more robust than current literature indicates.















NEUROLOGY 1998;50:684-688 © 1998 American Academy of Neurology





Creutzfeldt-Jakob disease in a husband and wife







P. Brown, MD, L. Cervenáková, MD, L. McShane, PhD, L. G. Goldfarb, MD, K. Bishop, BS, F. Bastian, MD, J. Kirkpatrick, MD, P. Piccardo, MD, B. Ghetti, MD and D. C. Gajdusek, MD From the Laboratory of CNS Studies (Drs. Brown, Cervenáková, Goldfarb, and Gajdusek), NINDS, and Biometric Research Branch (Dr. McShane), NCI, National Institutes of Health, Bethesda, MD; the Department of Obstetrics (K. Bishop), Gynecology and Reproductive Sciences, University of Texas Houston Health Science Center, Houston, TX; the Department of Pathology (Dr. Bastian), University of South Alabama Medical Center, Mobile, AL; the Department of Pathology (Dr. Kirkpatrick), The Methodist Hospital, Houston, TX; and the Department of Pathology (Drs. Piccardo and Ghetti), Indiana University School of Medicine, Indianapolis, IN.





Address correspondence and reprint requests to Dr. Paul Brown, Building 36, Room 5B21, National Institutes of Health, Bethesda, MD 20892.







A 53-year-old man died of sporadic Creutzfeldt-Jakob disease (CJD) after a 1.5-year clinical course. Four and a half years later, his then 55-year-old widow died from CJD after a 1-month illness. Both patients had typical clinical and neuropathologic features of the disease, and pathognomonic proteinase-resistant amyloid protein ("prion" protein, or PrP) was present in both brains. Neither patient had a family history of neurologic disease, and molecular genetic analysis of their PrP genes was normal. No medical, surgical, or dietary antecedent of CJD was identified; therefore, we are left with the unanswerable alternatives of human-to-human transmission or the chance occurrence of sporadic CJD in a husband and wife.





--------------------------------------------------------------------------------





Received May 5, 1997. Accepted in final form September 10, 1997.
















Research Lead: Dr. David Westaway, University of Alberta





Project: "Extending the spectrum of Prionopathies to Amyotrophic Lateral Sclerosis and Autism"







This project proposes to link the chemistry of the prion protein to the new territory of other nervous system diseases, such as ALS (Lou Gehrig's disease) and the socialization disorder autism-diseases which are at least one thousand times more common than prion diseases. It is believed that a different type or prion protein may operate in other types of brain diseases, which could lead to new ways of thinking about incurable disorders. The project will create changes in the amounts of the various forms of the new membrane protein, and then perform an array of analyses on the behavior and nervous system transmission of laboratory mice. Nervous transmission by electrical impulse can be measured in isolated brain cells, a system that is also convenient to study the effect of stress by adding small amounts of toxins to the fluids bathing the cultures. By these means, the project aims to extend the boundaries of what is considered "prion disease."





Funding: $520,500















Unfolding the Prion Mystery Building and Growing Research Expertise in Alberta Year 4 2008-2009 Annual Report





Dr. David Westaway, University of Alberta Extending the spectrum of prionopathies to amyotrophic lateral sclerosis (ALS) and autism Dr. Westaway’s study aims to extend the boundaries of what is considered prion disease. His project takes the chemistry of the prion protein into the territory of nervous system diseases such as ALS (Lou Gehrig’s disease) and socialization disorder diseases such as autism. These brain diseases are at least 1,000 times more common than diseases currently accepted as prion related. Dr. Westaway hypothesizes that a different type of protein misfolding may operate in brain diseases such as Lou Gehrig’s and autism. This type of protein misfolding may occur in response to stresses in the brain. Unlike misfolded prions, other misfolded proteins may be noninfectious and not viable outside of the affected animal. Dr. Westaway’s research team will investigate these hypotheses by inducing changes in the brain cells of laboratory mice, measuring the resulting electrical impulses in the animals’ nervous systems and analyzing the effect on behaviour. Because nervous transmission by electrical impulse can be measured in isolated brain cells, adding small amounts of toxins to the fluids bathing the cell cultures will make it possible to study the effect of stress. The results could lead to new ways of thinking about nervous system disorders.

















Published Date: 2011-10-03 19:22:21




Subject: PRO/AH/EDR> Prion disease update 2011 (09) Archive Number: 20111003.2983




PRION DISEASE UPDATE 2011 (09)




******************************




snip...




******




[6]





ALS a prion disease





Date: Tue 20 Sep 2011





Source: PrioNet Canada [abridged & edited]














A team of researchers from the University of British Columbia (BC) and the Vancouver Coastal Health Research Institute have found a key link between prions and the neurodegenerative disease ALS (Amyotrophic Lateral Sclerosis), also known as Lou Gehrig's disease. The discovery is significant as it opens the door to novel approaches to the treatment of ALS.





A pivotal paper published by the team this week in the Proceedings of the National Academy of Sciences (PNAS), demonstrates that the SOD1 protein (superoxide dismutase 1), which has been shown to be implicated in the ALS disease process, exhibits prion-like properties. The researchers found that SOD1 participates in a process called template-directed misfolding. This term refers to the coercion of one protein by another protein to change shape and accumulate in large complexes in a fashion similar to the process underlying prion diseases.





These findings provide a molecular explanation for the progressive spread of ALS through the nervous system, and highlight the central role of the propagation of misfolded proteins in the pathogenesis of neurodegenerative diseases, including ALS, Alzheimer's and Parkinson's.





"Our work has identified a specific molecular target, which when manipulated halts the conversion of the SOD1 protein to a misfolded, disease-causing form," says Dr. Neil Cashman, Scientific Director of PrioNet Canada, Canada Research Chair in Neurodegeneration and Protein Misfolding at UBC, and academic director of the Vancouver Coastal Health ALS Centre. "This discovery is a 1st-step toward the development of targeted treatments that may stop progression of ALS."





ALS is a progressive neuromuscular disease in which nerve cells die, resulting in paralysis and death. Approximately 500 to 3000 Canadians currently live with this fatal disease, for which there is no effective treatment yet.





"For many years, ALS has remained a complex puzzle, and we have found a key piece to help guide the research community to solutions," says Dr. Leslie Grad, a co-1st author of the project and current Manager of Scientific Programs at PrioNet Canada. "PrioNet is further exploring this discovery through newly-funded research projects."





The work was completed by Dr. Neil Cashman's lab at the Brain Research Centre based at the University of British Columbia and the Vancouver Coastal Health Research Institute, in collaboration with researchers at the University of Alberta. The research was supported by PrioNet Canada and in part by Amorfix Life Sciences and the Canadian Institutes of Health Research.





PrioNet Canada, based in Vancouver, has achieved international attention for scientific discoveries and risk management strategies directed at controlling prion diseases and is now directing capacity into therapeutic solutions for prion-like diseases of aging, such as Alzheimer's, Parkinson's and ALS.





[The paper referred to in the preceding press release above is entitled: Intermolecular transmission of superoxide dismutase 1 misfolding in living cells, by Leslie I. Grada and 9 others, Published in the Proceedings of the Academy of Sciences online before print in 19 Sept 2011, doi:10.1073/pnas.1102645108 http://www.pnas.org/content/early/2011/09/13/1102645108.abstract.






The Abstract reads as follows: "Human wild-type superoxide dismutase-1 (wtSOD1) is known to coaggregate with mutant SOD1 in familial amyotrophic lateral sclerosis (FALS), in double transgenic models of FALS, and in cell culture systems, but the structural determinants of this process are unclear. Here we molecularly dissect the effects of intracellular and cell-free obligately misfolded SOD1 mutant proteins on natively structured wild-type SOD1. Expression of the enzymatically inactive, natural familial ALS SOD1 mutations G127X and G85R in human mesenchymal and neural cell lines induces misfolding of wild-type natively structured SOD1, as indicated by: acquisition of immunoreactivity with SOD1 misfolding-specific monoclonal antibodies; markedly enhanced protease sensitivity suggestive of structural loosening; and nonnative disulfide-linked oligomer and multimer formation. Expression of G127X and G85R in mouse cell lines did not induce misfolding of murine wtSOD1, and a species restriction element for human wtSOD1 conversion was mapped to a region of sequence divergence in loop II and beta-strand 3 of the SOD1 beta-barrel (residues 24-36), then further refined surprisingly to a single tryptophan residue at codon 32 (W32) in human SOD1. Time course experiments enabled by W32 restriction revealed that G127X and misfolded wtSOD1 can induce misfolding of cell-endogenous wtSOD1. Finally, aggregated recombinant G127X is capable of inducing misfolding and protease sensitivity of recombinant human wtSOD1 in a cell-free system containing reducing and chelating agents; cell-free wtSOD1 conversion was also restricted by W32. These observations demonstrate that misfolded SOD1 can induce misfolding of natively structured wtSOD1 in a physiological intracellular milieu, consistent with a direct protein-protein interaction."







-- Communicated by: Terry S. Singeltary Sr. flounder9@verizon.net






[Prions are "misfolded" proteins, the infectious, aggregating agents in diseases such as Creutzfeldt-Jakob disease (CJD) in humans, chronic wasting disease (CWD) in deer and elk and bovine spongiform encephalopathy (BSE), also known as "mad cow‚" disease in cattle. In ALS, Alzheimer's and Parkinson's, the misfolded proteins are SOD1, beta-amyloid, and alpha-synuclein, respectively.





Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig 's disease in the United States and motor neuron disease (MND) in Europe, is a fatal neurodegenerative disease caused by deterioration of motor neurons in the brain and spinal cord. Individuals living with the disease experience progressive paralysis, as well as difficulty breathing or swallowing. At this time, no cure or effective treatment exists.





Recent research highlights links between the biological mechanisms of common neurological disorders, such as ALS, Alzheimer's and Parkinson's disease with prion disease. While each of these diseases manifests itself in a different way, the hallmark of each is a progressive accumulation of misfolded protein aggregates in the central nervous system. - Mod.CP]
















Tuesday, October 4, 2011


Alzheimer's disease is a Transmissible Spongiform Encephalopathy Prion disease


Molecular Psychiatry advance online publication 4 October 2011; doi: 10.1038/mp.2011.120













SCENARIO 4: ‘WE HAD OUR CHANCE AND WE BLEW IT’.


Unsustainable Production and Robust Markets.


Canada


Science


- Experimental evidence indicates that abnormal prions may persist for undetermined periods of time in buried materials.


- A new prion disease has occurred in cattle, possibly originated from CWD. Research funds are not available to investigate its nature and origin.


- The origin, transmission and prevalence of atypical BSE remain unclear.


- L-type atypical BSE has been demonstrated to be transmissible to humans.


- New testing procedures indicate the presence of sub-clinical carriers in the cattle population.


- New scientific knowledge provides no evidence that CWD is transmissible from Cervids to humans.















SNIP...SEE FULL TEXT ;.







Sunday, December 2, 2012.


CANADA 19 cases of mad cow disease SCENARIO 4: ‘WE HAD OUR CHANCE AND WE BLEW IT’.














Wednesday, May 16, 2012.



Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if?



Proposal ID: 29403.


















TSS

Wednesday, February 6, 2013

Penn study confirms no transmission of Alzheimer's proteins between humans ?




 




ONLINE FIRST

 


Evaluation of Potential Infectivity of Alzheimer and Parkinson Disease Proteins in Recipients of Cadaver-Derived Human Growth Hormone



David J. Irwin, MD; Joseph Y. Abrams, MPH; Lawrence B. Schonberger, MD, MPH; Ellen Werber Leschek, MD; James L. Mills, MD, MS; Virginia M.-Y. Lee, PhD, MBA; John Q. Trojanowski, MD, PhD JAMA Neurol. 2013;():1-7. doi:10.1001/jamaneurol.2013.1933.



Published online February 4, 2013



Importance Growing evidence of cell-to-cell transmission of neurodegenerative disease (ND)–associated proteins (NDAPs) (ie, tau, Aβ, and α-synuclein) suggests possible similarities to the infectious prion protein (PrPsc) in spongiform encephalopathies. There are limited data on the potential human-to-human transmission of NDAPs associated with Alzheimer disease (AD) and other non-PrPsc ND.



Objective To examine evidence for human-to-human transmission of AD, Parkinson disease (PD), and related NDAPs in cadaveric human growth hormone (c-hGH) recipients.



Design We conducted a detailed immunohistochemical analysis of pathological NDAPs other than PrPsc in human pituitary glands. We also searched for ND in recipients of pituitary-derived c-hGH by reviewing the National Hormone and Pituitary Program (NHPP) cohort database and medical literature.



Setting University-based academic center and agencies of the US Department of Health and Human Services.



Participants Thirty-four routine autopsy subjects (10 non-ND controls and 24 patients with ND) and a US cohort of c-hGH recipients in the NHPP.



Main Outcome Measures Detectable NDAPs in human pituitary sections and death certificate reports of non-PrPsc ND in the NHPP database.



Results We found mild amounts of pathological tau, Aβ, and α-synuclein deposits in the adeno/neurohypophysis of patients with ND and control patients. No cases of AD or PD were identified, and 3 deaths attributed to amyotrophic lateral sclerosis (ALS) were found among US NHPP c-hGH recipients, including 2 of the 796 decedents in the originally confirmed NHPP c-hGH cohort database.



Conclusions and Relevance Despite the likely frequent exposure of c-hGH recipients to NDAPs, and their markedly elevated risk of PrPsc-related disease, this population of NHPP c-hGH recipients does not appear to be at increased risk of AD or PD. We discovered 3 ALS cases of unclear significance among US c-hGH recipients despite the absence of pathological deposits of ALS-associated proteins (TDP-43, FUS, and ubiquilin) in human pituitary glands. In this unique in vivo model of human-to-human transmission, we found no evidence to support concerns that NDAPs underlying AD and PD transmit disease in humans despite evidence of their cell-to-cell transmission in model systems of these disorders. Further monitoring is required to confirm these conclusions.













"By interrogating an existing database with information on a cohort of well-characterized patients, we were able to determine that there is no evidence suggesting the pathology of Alzheimer's or Parkinson's can transmit between humans," said senior author John Q. Trojanowski, MD, PhD, professor of Pathology and Laboratory Medicine and co-director of the Penn Center for Neurodegenerative Disease Research." ...




 
 
 
 
really ???
 
 
 

 


Penn study confirms no transmission of Alzheimer's proteins between humans ?
 
 
 
Contact: Kim Menard kim.menard@uphs.upenn.edu 215-662-6183 University of Pennsylvania School of Medicine
 
 
 
 
Penn study confirms no transmission of Alzheimer's proteins between humans
 
 
 
 
 
PHILADELPHIA - Mounting evidence demonstrates that the pathological proteins linked to the onset and progression of neurodegenerative disorders are capable of spreading from cell-to-cell within the brains of affected individuals and thereby "spread" disease from one interconnected brain region to another. A new study found no evidence to support concerns that these abnormal disease proteins are "infectious" or transmitted from animals to humans or from one person to another. The study by researchers from the Perelman School of Medicine at the University of Pennsylvania, in conjunction with experts from the U.S. Centers for Disease Control and the Department of Health and Human Services, appears online in JAMA Neurology.
 
 
 
 
 
Cell-to-cell transmission is a potentially common pathway for disease spreading and progression in diseases like Alzheimer's (AD) and Parkinson's (PD) disease as well as frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS) and other related disorders. It appears that misfolded proteins spread from one cell to another and that the affected neurons become dysfunctional, while these toxic proteins go on to damage other regions of the brain over time.
 
 
 
 
"By interrogating an existing database with information on a cohort of well-characterized patients, we were able to determine that there is no evidence suggesting the pathology of Alzheimer's or Parkinson's can transmit between humans," said senior author John Q. Trojanowski, MD, PhD, professor of Pathology and Laboratory Medicine and co-director of the Penn Center for Neurodegenerative Disease Research. "We can now redouble efforts to find treatments, via immunotherapies or other approaches to stop the spreading of these toxic proteins between cells."
 
 
 
 
In order to verify whether such proteins could potentially be carried from person to person, the team of researchers analyzed data from an existing cohort of patients who had received human growth hormone (hGH) from cadaveric pituitary glands via a national program, as a beneficial treatment for stunted growth, before synthetic hGH was available. Nearly 7,700 patients were treated with cadaver-derived hGH (c-hGH) in the US between 1963 and 1985. In the mid-1980s, more than 200 patients worldwide who had received c-hGH inadvertently contaminated with prion proteins from affected donor pituitary tissue went on to develop an acquired form of Creutzfeldt-Jakob disease (CJD), a rare, degenerative, invariably fatal brain disorder caused by pathological prion proteins that also are the cause of Mad Cow disease. Since then, the cohort has been followed to track any additional cases of CJD, with extensive medical histories for patients over the 30+ years since the c-hGH therapy was stopped after the link to CJD was discovered in 1985.
 
In this current study, researchers looked for signs of an elevated risk of AD, PD, FTLD or ALS among this group and found that none of the c-hGH recipients developed AD, PD or FTLD. The team did identify three ALS cases of unclear significance, given that no traces of ALS disease proteins (TDP-43, FUS and Ubiquilin) were found in human pituitary glands, despite the presence of pathological AD (tau, Aβ) and PD (alpha-synuclein) proteins. This clarified that c-hGH recipients were most likely exposed to these neurodegenerative disease proteins linked to AD, PD and FTLD but this did not result in transmission of disease from person to person.
 
"This cohort is an invaluable resource and should continue to be followed, especially as we rapidly increase our understanding of disease progression in neurodegenerative conditions," said David Irwin, MD, lead author, and fellow in the Center for Neurodegenerative Disease Research and the department of Neurology in the Perelman School of Medicine.
 
###
 
 
The other co-authors of this study are Joseph Y. Abrams, Lawrence B. Schonberger, Ellen W. Leschek, James L. Mills, and Virginia M.-Y. Lee. This research was supported by grants from the National Institute on Aging (P30 AG010124, Alzheimer's Core Center grant, T32-AG000255), Intramural Research Program and National Institute of Child Health and Development at the National Institutes of Health.
 
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
 
The Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $479.3 million awarded in the 2011 fiscal year.
 
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
 
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2011, Penn Medicine provided $854 million to benefit our community.
 
 
 
 
 
 
Penn study confirms no transmission of Alzheimer's proteins between humans ?
 
 
 
confused ???
 
 
Greetings Jama, Penn state, Perelman School of Medicine Deans et al, eurekalert, Authors et al,
 
 
In my opinion, this subject title (NOT a transmission study, but only a study a team of researchers did by analyzed data from hGH recipients years, decades ago), and it’s interpretations, as described by Kim Menard
 
 
“Penn study confirms no transmission of Alzheimer's proteins between humans” ,
 
 
IN my opinion, is false.
 
 
In my opinion, this study does not prove or confirm that Alzheimer’s does not transmit to humans. your title is very misleading in my opinion. very confusing, as the title here stipulated from eurekalert. Penn state DID NOT confirm or prove that Alzheimer’s proteins are NOT transmissible between humans, of the contrary, there is indeed science showing that Alzheimer’s disease IS transmissible. I am very close to all this, please see ;
 
 
Penn Study: Transmission of Tangles in Alzheimer's Mice Provides More Authentic Model of Tau Pathology
 
 
 
January 16, 2013
 
 
 
snip...
 
 
 
The study demonstrates that synthetic tau fibrils alone are capable of inducing authentic NFT-like tau clumps and initiating spreading of tau pathology in an Alzheimer’s mouse model.
 
 
 
 
 
 
Transmission of Tangles in Alzheimer's Mice Provides More Authentic Model of Tau Pathology, Penn Study Shows
 
 
New Model Provides First Step in Generating New Therapies
 
 
 
 
 
please see my source reference below ;
 
 
Ann N Y Acad Sci. 1982;396:131-43.
 
 
Alzheimer's disease and transmissible virus dementia (Creutzfeldt-Jakob disease).
 
 
 
Brown P, Salazar AM, Gibbs CJ Jr, Gajdusek DC.
 
 
Abstract
 
 
Ample justification exists on clinical, pathologic, and biologic grounds for considering a similar pathogenesis for AD and the spongiform virus encephalopathies. However, the crux of the comparison rests squarely on results of attempts to transmit AD to experimental animals, and these results have not as yet validated a common etiology. Investigations of the biologic similarities between AD and the spongiform virus encephalopathies proceed in several laboratories, and our own observation of inoculated animals will be continued in the hope that incubation periods for AD may be even longer than those of CJD.
 
 
 
 
 
CJD1/9 0185
Ref: 1M51A
 
IN STRICT CONFIDENCE
 
Dr McGovern 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 p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegenerative 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
 
 
 
 
 
BSE101/1 0136
 
 
IN CONFIDENCE
 
 
5 NOV 1992
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 recognized 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 emphasizes 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
BSE101/1 0137
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.
JS METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832
121/YdeS
92/11.4/1.2
 
 
 
 
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
 
 
 
 
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
 
 
 
 
 
Wednesday, January 5, 2011
 
 
ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions
 
 
David W. Colby1,* and Stanley B. Prusiner1,2
 
 
 
 
 
Tuesday, October 4, 2011
Molecular Psychiatry
advance online publication 4 October 2011; doi: 10.1038/mp.2011.120
 
 
De novo induction of amyloid-ß deposition in vivo
 
 
Our results suggest that some of the typical brain abnormalities associated with AD can be induced by a prion-like mechanism of disease transmission through propagation of protein misfolding. These findings may have broad implications for understanding the molecular mechanisms responsible for the initiation of AD, and may contribute to the development of new strategies for disease prevention and intervention. Keywords: amyloid; prion; protein misfolding; disease transmission
 
 
 
 
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
 
 
Background
 
 
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease have both been around a long time, and was discovered in or around the same time frame, early 1900’s. Both diseases are incurable and debilitating brain disease, that are in the end, 100% fatal, with the incubation/clinical period of the Alzheimer’s disease being longer (most of the time) than the TSE prion disease. Symptoms are very similar, and pathology is very similar.
 
 
Methods
 
 
Through years of research, as a layperson, of peer review journals, transmission studies, and observations of loved ones and friends that have died from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant Creutzfelt Jakob Disease CJD.
 
 
Results
 
 
I propose that Alzheimer’s is a TSE disease of low dose, slow, and long incubation disease, and that Alzheimer’s is Transmissible, and is a threat to the public via the many Iatrogenic routes and sources. It was said long ago that the only thing that disputes this, is Alzheimer’s disease transmissibility, or the lack of. The likelihood of many victims of Alzheimer’s disease from the many different Iatrogenic routes and modes of transmission as with the TSE prion disease.
 
 
Conclusions
 
 
There should be a Global Congressional Science round table event set up immediately to address these concerns from the many potential routes and sources of the TSE prion disease, including Alzheimer’s disease, and a emergency global doctrine put into effect to help combat the spread of Alzheimer’s disease via the medical, surgical, dental, tissue, and blood arena’s. All human and animal TSE prion disease, including Alzheimer’s should be made reportable in every state, and Internationally, WITH NO age restrictions. Until a proven method of decontamination and autoclaving is proven, and put forth in use universally, in all hospitals and medical, surgical arena’s, or the TSE prion agent will continue to spread. IF we wait until science and corporate politicians wait until politics lets science _prove_ this once and for all, and set forth regulations there from, we will all be exposed to the TSE Prion agents, if that has not happened already.
 
 
end...tss
 
 
Wednesday, May 16, 2012
 
 
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
 
 
Proposal ID: 29403
 
 
 
 
 
UPDATE JUNE 28, 2012
 
 
Scottish TSE Network November Symposium Announcement Event: 12 November 2012
 
 
Chair: Prof Hugh Perry, University of Southampton, Southampton UK
Location: The Roslin Institute Building Auditorium
If you would like to book a place at this event, please let Gila Holliman know.
Cost: £125.
 
 
Title: Is Alzheimer’s Disease a transmissible disease?
 
 
Speakers:
 
 
Session 1:
Prof Bob Will, National CJD Surveillance Unit, Edinburgh UK
Prof James Ironside, National CJD Surveillance Unit, Edinburgh UK
Prof Lary Walker, Emory School of Medicine, Atlanta USA
 
Session 2:
 
 
Prof Mathias Jucker, Hertie Institute for Clinical Brain Research, Stuttgart Germany
Prof William Van Nostrand, Stony Brook University, Stony Brook USA
Dr Claudio Soto, University of Texas Medical School, Houston USA
 
Session 3:
 
 
Dr Fabrizio Tagliavini, Instituto Neurologico Carlo Besta, Milan Italy
Prof Pedro Piccardo, Food and Drug Administration, Washington DC USA
Dr Bruce Chesebro, National Institutes of Health, Missoula USA
 
 
 
 
Friday, September 3, 2010
 
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE
 
 
 
Wednesday, September 21, 2011
 
PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS)
 
 
 
 
SCENARIO 3: ‘THE THIN STEMMED GLASS’
 
 
... a TSE is found that is linked to Alzheimer’s disease.
 
 
 
 
 
Thursday, January 17, 2013
 
TSE guidance, surgical, dental, blood risk factors, Part 4 Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings (updated January 2013)
 
 
 
 
Monday, January 14, 2013
 
Gambetti et al USA Prion Unit change another highly suspect USA mad cow victim to another fake name i.e. sporadic FFI at age 16 CJD Foundation goes along with this BSe
 
 
 
Monday, December 31, 2012
 
Creutzfeldt Jakob Disease and Human TSE Prion Disease in Washington State, 2006–2011-2012
 
 
 
Saturday, December 29, 2012
 
MAD COW USA HUMAN TSE PRION DISEASE DECEMBER 29 2012 CJD CASE LAB REPORT
 
 
 
Tuesday, December 25, 2012
 
CREUTZFELDT JAKOB TSE PRION DISEASE HUMANS END OF YEAR REVIEW DECEMBER 25, 2012
 
 
 
Friday, November 23, 2012
 
sporadic Creutzfeldt-Jakob Disease update As at 5th November 2012 UK, USA, AND CANADA
 
 
 
Letters
 
JAMA. 2001;285(6):733-734. doi: 10.1001/jama.285.6.733
 
 
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
 
 
Terry S. Singeltary, Sr Bacliff, Tex
 
 
Since this article does not have an abstract, we have provided the first 150 words of the full text.
 
KEYWORDS: creutzfeldt-jakob disease, diagnosis. To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
 
 
References 1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
 
 
 
Published March 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Terry S. Singeltary, retired (medically)
 
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?
 
Published March 26, 2003
 
 
 
THE PATHOLOGICAL PROTEIN
BY Philip Yam
Yam Philip Yam News Editor Scientific American www.sciam.com
Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.
CHAPTER 14
Laying Odds
 
 
Are prion diseases more prevalent than we thought?
 
 
Researchers and government officials badly underestimated the threat that mad cow disease posed when it first appeared in Britain. They didn't think bovine spongiform encephalopathy was a zoonosis-an animal disease that can sicken people. The 1996 news that BSE could infect humans with a new form of Creutzfeldt-Jakob disease stunned the world. It also got some biomedical researchers wondering whether sporadic CJD may really be a manifestation of a zoonotic sickness. Might it be caused by the ingestion of prions, as variant CJD is?
 
 
Revisiting Sporadic CJD
 
 
It's not hard to get Terry Singeltary going. "I have my conspiracy theories," admitted the 49-year-old Texan.1 Singeltary is probably the nation's most relentless consumer advocate when it comes to issues in prion diseases. He has helped families learn about the sickness and coordinated efforts with support groups such as CJD Voice and the CJD Foundation. He has also connected with others who are critical of the American way of handling the threat of prion diseases. Such critics include Consumers Union's Michael Hansen, journalist John Stauber, and Thomas Pringle, who used to run the voluminous www.madcow. org Web site. These three lend their expertise to newspaper and magazine stories about prion diseases, and they usually argue that prions represent more of a threat than people realize, and that the government has responded poorly to the dangers because it is more concerned about protecting the beef industry than people's health.
 
 
Singeltary has similar inclinations. ...
 
 
snip...
 
 
THE PATHOLOGICAL PROTEIN
 
Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9
 
June 2003
BY Philip Yam
 
 
CHAPTER 14 LAYING ODDS
 
 
Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.
 
 
 
 
 
 
 
 
 
 
 
14th ICID International Scientific Exchange Brochure -
 
Final Abstract Number: ISE.114
 
Session: International Scientific Exchange
 
 
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009
 
 
T. Singeltary
 
Bacliff, TX, USA
 
Background:
 
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
 
Methods:
 
 
12 years independent research of available data
 
Results:
 
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
 
Conclusion:
 
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
 
 
 
Article
 
Human Prion Diseases in the United States
 
 
Robert C. Holman mail,
Ermias D. Belay,
Krista Y. Christensen,
Ryan A. Maddox,
Arialdi M. Minino,
Arianne M. Folkema,
Dana L. Haberling,
Teresa A. Hammett,
Kenneth D. Kochanek,
James J. Sejvar,
Lawrence B. Schonberger
 
 
 
 
 
 
 
 
CJD Singeltary submission to PLOS ;
No competing interests declared.
new link url ;
 
 
 
 
with kindest regards,
terry
MOM RIP 12/14/97 confirmed Heidenhain Variant Creutzfeldt Jakob Disease and her MOM and Brother died with Alzheimer’s...I can’t wait to see what happens...not.
layperson
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518