Tuesday, January 26, 2016

Alzheimer-type brain pathology may be transmitted by grafts of dura mater

Alzheimer-type brain pathology may be transmitted by grafts of dura mater

 

26/01/2016 By Karl Frontzek, et al.: Alzheimer’s disease is characterized by progressive dementia and brain plaques consisting of the Aβ protein. Conventional wisdom has it that Alzheimer’s disease is not a transmissible disease. However, plaques recovered from brains of Alzheimer’s disease patients were repeatedly found to induce further plaques when injected into the brains of laboratory mice, suggesting that transmission may actually occur.

 

Reporting in today’s Swiss Medical Weekly, Karl Frontzek and colleagues (University of Zurich and Vienna Medical University) have investigated individuals who received brain grafts of dura mater during neurosurgery. The dura mater (“tough mother”) is the leathery membrane covering the brain and spinal cord. Such grafts were necessary to allow the brain to heal after surgery. Tragically, some of the dura mater donors were infected with prions (the agents causing the fatal Creutzfeldt-Jakob disease), and the grafting procedure transmitted the disease to the recipients.

 

Frontzek and colleagues now report the presence of Aβ plaques in 5 of 7 brains of relatively young recipients of dura mater grafts who succumbed to Creutzfeldt-Jakob disease. Aβ plaques were detected much more frequently than in brains of people who did not receive any dura mater grafts. Aβ plaques are highly unusual in young individuals and may have been caused by the dural grafts. This study adds to the evidence that the hallmarks of Alzheimer’s disease may indeed be transmissible under certain circumstances, and calls for heightened attention to an unexpected, potentially very serious problem of transplantation medicine.

 

>> Read the article

 

This is a summary of a paper that was published on www.smw.ch. Must be cited as: Frontzek K, Lutz MI, Aguzzi A, Kovacs GG, Budka H. Amyloid-β pathology and cerebral amyloid angiopathy are frequent in iatrogenic Creutzfeldt-Jakob disease after dural grafting. Swiss Med Wkly. 2016;146:w14287.

 


 

Original article | Published 26 January 2016, doi:10.4414/smw.2016.14287

 

Cite this as: Swiss Med Wkly. 2016;146:w14287

 

Amyloid-β pathology and cerebral amyloid angiopathy are frequent in iatrogenic Creutzfeldt-Jakob disease after dural grafting

 

Karl Frontzeka, Mirjam I. Lutzb, Adriano Aguzzia, Gabor G. Kovacsb *, Herbert Budkaa,b *

 

a Institute of Neuropathology, University Hospital Zurich, Switzerland b Institute of Neurology, Medical University Vienna, Austria * These authors contributed equally

 

 Summary

 

QUESTIONS UNDER STUDY: Alzheimer-type amyloid-β (Aβ) pathology was reported in brains of individuals developing iatrogenic Creutzfeldt-Jakob disease (iCJD) after treatment with human cadaveric growth hormone, and interpreted as evidence of human transmission of Aβ by the treatment. Here we investigated the prevalence of Aβ pathology in other instances of iCJD related to dura mater grafts.

 

 METHODS: By use of immunohistochemistry for Aβ, we investigated seven brains of patients (age range 28–63) who succumbed to iCJD after dural grafting, which had been applied by means of neurosurgery between 11 and 25 years before death. For control, we examined a series of 21 brains of age-matched (40–63 years) patients with sporadic CJD (sCJD) and an additional series of 81 sCJD cases (55–85 years) with the same methods.

 

 RESULTS: In five of seven iCJD brains, Aβ was deposited in meningeal vessels as congophilic amyloid angiopathy and brain parenchymal plaques. This was significantly (p <0 .001="" age-matched="" and="" controls="" div="" frequent="" in="" more="" scjd="" series.="" than="" the="" usual="">
 

 CONCLUSIONS: We conclude that congophilic amyloid angiopathy and brain parenchymal Aβ plaques are frequent in iCJD after dural grafting. The presence of Aβ pathology in young individuals is highly unusual and suggests a causal relationship to the dural grafts. Further studies will be needed to elucidate whether such pathology resulted from the seeding of Aβ aggregates from the grafts to host tissues.

 

 Key words: prion; iatrogenic Creutzfeldt-Jakob disease; amyloid-beta; Alzheimer pathology; prion-like propagation; dural grafting

 

Introduction...

 

snip...

 

Discussion We report here that CAA and brain parenchymal Aβ plaques are frequent in iCJD after dural grafting, even in young individuals. Similarly to what was previously reported in iCJD after hGH treatment [15], we failed to detect any marked tau pathology in our series after dural grafting. The presence of Aβ pathology in young individuals who present with neither a family history of early-onset dementia or prominent AD-related tau pathology is highly unusual and suggests a causal relationship to the dural grafts [19]. It is plausible that such pathology may have resulted from the seeding of Aβ aggregates from the grafts to host tissues, yet alternative explanations are also possible.

 

The Aβ pathology was observed many years after neurosurgery that applied a graft of dura mater. It is intriguing that all cases with particularly long intervals after dural grafting (more than 20 years) were the five who had Aβ pathology, whereas the two brains without Aβ had much shorter intervals of 11 and 12 years, respectively. This does not seem to be a function of age, as both cases without Aβ had ages in the 50s, whereas Aβ brains included three cases younger than 50. Such prolonged incubation over decades would be another striking similarity with prion diseases. As data on the site of the applied dural graft were not available for all cases, we were unable to investigate conclusively whether the severity of the induced Aβ pathology had a topographic relationship to the site of grafting. For the same reason, it was not possible to assert any local difference between meningeal vs parenchymal Aβ according to graft site.

 

The clinical signs and symptoms in all patients reported here were typical of CJD [3]; there was no report of previous mild or slowly progressive cognitive impairment that might have been the result of Aβ pathology prior to the onset of rapidly progressive iCJD. All brains had prominent and widespread deposition of PrPSc; in comparison, Aβ was less prominent. Thus, any striking local co-occurrence suggestive of potential cross-seeding was not discernible.

 

The findings reported here extend a previous study of iCJD after hGH treatment [15] and suggest that both human dural tissue grafts and pituitary extracts are able to elicit Aβ pathology decades later. This would be in agreement with ample evidence of prion-like propagation of aggregated proteins in animal models of neurodegeneration [8]. However, as discussed previously [16], it is currently impossible to eliminate the possibility that head trauma or the underlying conditions which had led to dural grafting, or neurosurgery, may have contributed to the induction of Aβ pathology.

 

A previous study [20] demonstrated the presence of Aβ in human pituitary tissue, the source of prion-contaminated hGH preparations. However, no clinically manifest cases of AD or PD were identified among recipients of pituitary-derived hGH in review of the large US National Hormone and Pituitary Program cohort database [20]. Hence, further studies are needed to elucidate whether potential transmission and propagation of Aβ – and of other neurodegeneration-related proteins – from external sources is indeed able to induce a clinically manifest human disease.

 

Whilst the iatrogenic transmission of aggregated Aβ is one of several possible explanations for the findings reported here, the growing circumstantial evidence for such transmission should prompt a critical re-evaluation of the decontamination procedures for surgical instruments and drugs of biological origin, with the goal to ensure the complete absence of potentially transmissible contaminants.

 

Disclosure statement: We declare no competing interests.This research received no specific grant from any funding agency in the commercial or not-for-profit sectors. The national CJD surveillance in Switzerland and Austria, as performed by the respective National Reference Centres for Human Prion Diseases (NRPE, located at the Institute of Neuropathology, University Hospital Zurich, and ÖRPE, located at the Institute of Neurology, Medical University Vienna) is supported by the Federal Office of Public Health in Berne, Switzerland, and the Federal Ministry of Health in Vienna, Austria, respectively.

 

Correspondence: Herbert Budka, Institute of Neuropathology, University Hospital Zurich, Schmelzbergstr. 12, CH-8091 Zurich, Switzerland, herbert.budka[at]usz.ch

 

References snip...end

 


 

Evidence for human transmission of amyloid-? pathology and cerebral amyloid angiopathy

 

07 02:27 AM

 

Terry S. Singeltary Sr. said:

 

re-Evidence for human transmission of amyloid-? pathology and cerebral amyloid angiopathy

 

2015-12-07 02:27 AM

 

Terry S. Singeltary Sr. said: re-Evidence for human transmission of amyloid-? 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)

 


 

I would kindly like to comment on the Nature Paper, the Lancet reply, and the newspaper articles.

 

First, I applaud Nature, the Scientist and Authors of the Nature paper, for bringing this important finding to the attention of the public domain, and the media for printing said findings.

 

Secondly, it seems once again, politics is getting in the way possibly of more important Transmissible Spongiform Encephalopathy TSE Prion scientific findings. findings that could have great implications for human health, and great implications for the medical surgical arena. but apparently, the government peer review process, of the peer review science, tries to intervene again to water down said disturbing findings.

 

where have we all heard this before? it?s been well documented via the BSE Inquiry. have they not learned a lesson from the last time?

 

we have seen this time and time again in England (and other Country?s) with the BSE mad cow TSE Prion debacle.

 

That ?anonymous' Lancet editorial was disgraceful. The editor, Dick Horton is not a scientist.

 

The pituitary cadavers were very likely elderly and among them some were on their way to CJD or Alzheimer's. Not a bit unusual. Then the recipients ? who got pooled extracts injected from thousands of cadavers ? were 100% certain to have been injected with both seeds. No surprise that they got both diseases going after thirty year incubations.

 

That the UK has a "system in place to assist science journalists" to squash embargoed science reports they find ?alarming? is pathetic.

 

Sounds like the journalists had it right in the first place: ?Alzheimer?s may be a transmissible infection? in The Independent to ?You can catch Alzheimer?s? in The Daily Mirror or ?Alzheimer?s bombshell" in The Daily Express

 

if not for the journalist, the layperson would not know about these important findings.

 

where would we be today with sound science, from where we were 30 years ago, if not for the cloak of secrecy and save the industry at all cost mentality?

 

when you have a peer review system for science, from which a government constantly circumvents, then you have a problem with science, and humans die.

 

to date, as far as documented body bag count, with all TSE prion named to date, that count is still relatively low (one was too many in my case, Mom hvCJD), however that changes drastically once the TSE Prion link is made with Alzheimer?s, the price of poker goes up drastically.

 

so, who makes that final decision, and how many more decades do we have to wait?

 

the iatrogenic mode of transmission of TSE prion, the many routes there from, load factor, threshold from said load factor to sub-clinical disease, to clinical disease, to death, much time is there to spread a TSE Prion to anywhere, but whom, by whom, and when, do we make that final decision to do something about it globally? how many documented body bags does it take? how many more decades do we wait? how many names can we make up for one disease, TSE prion?

 

Professor Collinge et al, and others, have had troubles in the past with the Government meddling in scientific findings, that might in some way involve industry, never mind human and or animal health.

 

FOR any government to continue to circumvent science for monetary gain, fear factor, or any reason, shame, shame on you.

 

in my opinion, it?s one of the reasons we are at where we are at to date, with regards to the TSE Prion disease science i.e. money, industry, politics, then comes science, in that order.

 

greed, corporate, lobbyist there from, and government, must be removed from the peer review process of sound science, it?s bad enough having them in the pharmaceutical aspect of healthcare policy making, in my opinion.

 

my mother died from confirmed hvCJD, and her brother (my uncle) Alzheimer?s of some type (no autopsy?). just made a promise, never forget, and never let them forget, before I do.

 

I kindly wish to remind the public of the past, and a possible future we all hopes never happens again. ...

 

[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.]

 


 


 


 

Terry S. Singeltary Sr. Bacliff, Texas USA 77518

 

snip...see Singeltary comment ;

 


 

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 ?

 

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

 


 

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.

 

 

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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.

 


 

Friday, January 10, 2014

 

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???

 

Greetings Friends, Neighbors, and Colleagues,

 


 

Thursday, January 14, 2016

 

Preventable Tragedies: Superbugs and How Ineffective Monitoring of Medical Device Safety Fails Patients REPORT

 

how can it be, HOW CAN IT BE $$$ not a word about CJD GSS FFI VPSPR TSE Prions that I saw...absolutely crazy, WE ARE MISSING THE BIGGER PICTURE!

 

how many victims that will never be reported ???

 


 

Sunday, January 17, 2016

 

Of Grave Concern Heidenhain Variant Creutzfeldt Jakob Disease

 


 

kind regards, terry

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