Bill Gates makes $100 million personal investment to fight Alzheimer's
Kate Kelland, Health, Science Correspondent 5 MIN READ LONDON, Nov 13 (Reuters) - Billionaire Microsoft co-founder Bill Gates is to invest $50 million in the Dementia Discovery Fund, a venture capital fund that brings together industry and government to seek treatments for the brain-wasting disease.
FILE PHOTO: Microsoft founder Bill Gates looks on during a healthcare event in Brussels, Belgium, February 16, 2017. REUTERS/Eric Vidal/File Photo The investment - a personal one and not part of Gates’ philanthropic Bill & Melinda Gates Foundation - will be followed by another $50 million in start-up ventures working in Alzheimer’s research, Gates said.
With rapidly rising numbers of people suffering from Alzheimer’s and other forms of dementia, the disease is taking a growing emotional and financial toll as people live longer, Gates told Reuters in an interview.
“It’s a huge problem, a growing problem, and the scale of the tragedy - even for the people who stay alive - is very high,” he said.
Despite decades of scientific research, there is no treatment that can slow the progression of Alzheimer‘s. Current drugs can do no more than ease some of the symptoms.
Gates said, however, that with focused and well-funded innovation, he’s “optimistic” treatments can be found, even if they might be more than a decade away.
”It’ll take probably 10 years before new theories are tried enough times to give them a high chance of success. So it’s very hard to hazard a guess (when an effective drug might be developed).
“I hope that in the next 10 years that we have some powerful drugs, but it’s possible that won’t be achieved.”
Dementia, of which Alzheimer’s is the most common form, affects close to 50 million people worldwide and is expected to affect more than 131 million by 2050, according to the non-profit campaign group Alzheimer’s Disease International.
FILE PHOTO: Microsoft co-founder and philanthropist Bill Gates talks with a colleague before the Berkshire Hathaway annual meeting in Omaha, Nebraska, U.S. May 6, 2017. REUTERS/Rick Wilking/File Photo The DDF, which was launched in 2015 and involves drugmakers GlaxoSmithKline, Johnson & Johnson, Eli Lilly, Pfizer and Biogen Idec as well as the UK government, has already invested in at least nine start-up companies investigating potential ways to stop or reverse the biological processes that lead to dementia.
Gates told Reuters the additional $50 million would be put into start-ups working on some “less mainstream” approaches to the disease, but said he had not yet identified these companies.
The philanthropist, whose usual focus is on infectious diseases in poorer countries, said Alzheimer’s caught his interest partly for personal reasons, and partly because it has so far proved such a tough nut to crack.
“I know how awful it is to watch people you love struggle as the disease robs them of their mental capacity ... It feels a lot like you’re experiencing a gradual death of the person that you knew,” he said in a blog post about the dementia investments.
”Some of the men in my family have suffered from Alzheimer‘s, but I wouldn’t say that’s the sole reason“ (for this investment),” he added.
Jeremy Hughes, chief executive of the Alzheimer’s Society charity, welcomed Gates’ “significant personal investment”, saying it would speed up progress toward a cure and help reduce stigma around dementia: “With Bill Gates now joining all those already united against dementia, there is new hope for advances in the care and cure of dementia,” he said in a statement.
Through talking to experts in the field over the past year, Gates said he had identified five areas of need: Understanding better how Alzheimer’s unfolds, detecting and diagnosing it earlier, pursuing multiple approaches to trying to halt the disease, making it easier for people to take part in clinical trials of potential new medicines, and using data better.
“My background at Microsoft and my (Gates) Foundation background say to me that a data-driven contribution might be an area where I can help add some value,” he said.
Alongside the $50 million investment in DDF and the additional $50 million planned for start-ups, Gates said he would like to award a grant to build a global dementia data platform. This would make it easier for researchers to look for patterns and identify new pathways for treatment, he said.
Editing by Dan Grebler and Andrew Heavens Our Standards:The Thomson Reuters Trust Principles.
OUTSTANDING MR AND MRS GATES! MANY THANKS!
let's not forget the elephant in the room. curing Alzheimer's would be a great and wonderful thing, but for starters, why not start with the obvious, lets prove the cause or causes, and then start to stop that. think iatrogenic, friendly fire, or the pass it forward mode of transmission. think medical, surgical, dental, tissue, blood, related transmission. think transmissible spongiform encephalopathy aka tse prion disease aka mad cow type disease...
Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies
Original Article
Molecular Psychiatry , (31 October 2017) | doi:10.1038/mp.2017.204
Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies
X-L Bu, Y Xiang, W-S Jin, J Wang, L-L Shen, Z-L Huang, K Zhang, Y-H Liu, F Zeng, J-H Liu, H-L Sun, Z-Q Zhuang, S-H Chen, X-Q Yao, B Giunta, Y-C Shan, J Tan, X-W Chen, Z-F Dong, H-D Zhou, X-F Zhou, W Song and Y-J Wang
Abstract
The amyloid-β protein (Aβ) protein plays a pivotal role in the pathogenesis of Alzheimer’s disease (AD). It is believed that Aβ deposited in the brain originates from the brain tissue itself. However, Aβ is generated in both brain and peripheral tissues. Whether circulating Aβ contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aβ originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aβ plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aβ accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aβ can enter the brain, form the Aβ-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aβ metabolism in both the brain and the periphery.
MONDAY, NOVEMBER 06, 2017
Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque
''On secondary and tertiary transmissions, however, the proportion of PrPres positive animals gradually increased to almost 100%. Recent communications suggest that a similar situation might exist in other models of experimental exposure to prions involving swine32 and cattle33. ''
''Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque''
Friday, January 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???
Alzheimer’s disease, iatrogenic, and Transmissible Spongiform Encephalopathy TSE Prion disease, that is the question ???
>>> The only tenable public line will be that "more research is required’’ <<<
>>> possibility on a transmissible prion remains open<<<
O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?
[9. Whilst this matter is not at the moment directly concerned with the iatrogenic CJD cases from hgH, there remains a possibility of litigation here, and this presents an added complication. There are also results to be made available shortly (1) concerning a farmer with CJD who had BSE animals, (2) on the possible transmissibility of Alzheimer’s and (3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest.]
snip...see full Singeltary Nature comment here;
see Singeltary comments to Plos ;
Subject: 1992 IN CONFIDENCE TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES POSSIBILITY ON A TRANSMISSIBLE PRION REMAINS OPEN
BSE101/1 0136
IN CONFIDENCE
CMO
From: . Dr J S Metiers DCMO 4
November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognised the public sensitivity of these findings and intend to report them in their proper context. 'This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.
2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed". As the report emphasises the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible. what are the implications for public health?
3. The route 'of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process. Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk.
However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed. 1
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.
J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832 llllYc!eS 2 92/11.4/1.2
>>> The only tenable public line will be that "more research is required’’ <<<
>>> possibility on a transmissible prion remains open<<<
O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?
Re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)
snip...see full Singeltary Nature comment here;
Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease
*** Singeltary comment PLoS ***
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Posted by flounder on 05 Nov 2014 at 21:27 GMT
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.
Sunday, November 22, 2015
*** Effect of heating on the stability of amyloid A (AA) fibrils and the intra- and cross-species transmission of AA amyloidosis
Abstract
Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by extracellular deposition of AA fibrils. AA fibrils are found in several tissues from food animals with AA amyloidosis. For hygienic purposes, heating is widely used to inactivate microbes in food, but it is uncertain whether heating is sufficient to inactivate AA fibrils and prevent intra- or cross-species transmission. We examined the effect of heating (at 60 °C or 100 °C) and autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western blot analysis, transmission electron microscopy (TEM), and mouse model transmission experiments. TEM revealed that a mixture of AA fibrils and amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at 135 °C produced large amorphous aggregates. AA fibrils retained antigen specificity in Western blot analysis when heated at 100 °C or autoclaved at 121 °C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA fibrils at 121 °C or 135 °C significantly decreased amyloid deposition. Moreover, amyloid deposition in mice injected with murine AA fibrils was more severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These results suggest that AA fibrils are relatively heat stable and that similar to prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA fibrils. These findings may contribute to the prevention of AA fibril transmission through food materials to different animals and especially to humans.
Purchase options Price * Issue Purchase USD 511.00 Article Purchase USD 54.00
*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery ***
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA Diagnosis and Reporting of Creutzfeldt-Jakob Disease
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.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
Tracking spongiform encephalopathies in North America
Xavier Bosch
Published: August 2003
Summary;
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.”
49-year-old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease (CJD). So he decided to gather hundreds of documents on transmissible spongiform encephalopathies (TSE) and realised that if Britons could get variant CJD from bovine spongiform encephalopathy (BSE), Americans might get a similar disorder from chronic wasting disease (CWD) the relative of mad cow disease seen among deer and elk in the USA. Although his feverish search did not lead him to the smoking gun linking CWD to a similar disease in North American people, it did uncover a largely disappointing situation.
Singeltary was greatly demoralised at the few attempts to monitor the occurrence of CJD and CWD in the USA. Only a few states have made CJD reportable. Human and animal TSEs should be reportable nationwide and internationally, he complained in a letter to the Journal of the American Medical Association (JAMA 2003; 285: 733). "I hope that the CDC does not continue to expect us to still believe that the 85% plus of all CJD cases which are sporadic are all spontaneous, without route or source."
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
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.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
Until recently, CWD was thought to be confined to the wild in a small region in Colorado. But since early 2002, it has been reported in other areas, including Wisconsin, South Dakota, and the Canadian province of Saskatchewan. Indeed, the occurrence of CWD in states that were not endemic previously increased concern about a widespread outbreak and possible transmission to people and cattle.
To date, experimental studies have proven that the CWD agent can be transmitted to cattle by intracerebral inoculation and that it can cross the mucous membranes of the digestive tract to initiate infection in lymphoid tissue before invasion of the central nervous system. Yet the plausibility of CWD spreading to people has remained elusive.
Part of the problem seems to stem from the US surveillance system. CJD is only reported in those areas known to be endemic foci of CWD. Moreover, US authorities have been criticised for not having performed enough prionic tests in farm deer and elk.
Although in November last year the US Food and Drug Administration issued a directive to state public-health and agriculture officials prohibiting material from CWD-positive animals from being used as an ingredient in feed for any animal species, epidemiological control and research in the USA has been quite different from the situation in the UK and Europe regarding BSE.
"Getting data on TSEs in the USA from the government is like pulling teeth", Singeltary argues. "You get it when they want you to have it, and only what they want you to have."
Norman Foster, director of the Cognitive Disorders Clinic at the University of Michigan (Ann Arbor, MI, USA), says that "current surveillance of prion disease in people in the USA is inadequate to detect whether CWD is occurring in human beings"; adding that, "the cases that we know about are reassuring, because they do not suggest the appearance of a new variant of CJD in the USA or atypical features in patients that might be exposed to CWD. However, until we establish a system that identifies and analyses a high proportion of suspected prion disease cases we will not know for sure". The USA should develop a system modelled on that established in the UK, he points out.
Ali Samii, a neurologist at Seattle VA Medical Center who recently reported the cases of three hunters "two of whom were friends" who died from pathologically confirmed CJD, says that "at present there are insufficient data to claim transmission of CWD into humans"; adding that "[only] by asking [the questions of venison consumption and deer/elk hunting] in every case can we collect suspect cases and look into the plausibility of transmission further". Samii argues that by making both doctors and hunters more aware of the possibility of prions spreading through eating venison, doctors treating hunters with dementia can consider a possible prion disease, and doctors treating CJD patients will know to ask whether they ate venison.
CDC spokesman Ermias Belay says that the CDC "will not be investigating the [Samii] cases because there is no evidence that the men ate CWD-infected meat". He notes that although "the likelihood of CWD jumping the species barrier to infect humans cannot be ruled out 100%" and that "[we] cannot be 100% sure that CWD does not exist in humans& the data seeking evidence of CWD transmission to humans have been very limited".
26 March 2003
Terry S. Singeltary, retired (medically) CJD WATCH
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?
2 January 2000 British Medical Journal U.S.
Scientist should be concerned with a CJD epidemic in the U.S., as well
15 November 1999 British Medical Journal hvCJD in the USA * BSE in U.S.
*** U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
2001 FDA CJD TSE Prion Singeltary Submission
THURSDAY, AUGUST 17, 2017
*** Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States revisited 2017 Singeltary et al
THURSDAY, AUGUST 10, 2017
Minimise transmission risk of CJD and vCJD in healthcare settings Updated 10 August 2017
WEDNESDAY, NOVEMBER 1, 2017
Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies
Terry S. Singeltary Sr.
