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? its 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 Countrys) 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: ?Alzheimers
may be a transmissible infection? in The Independent to ?You can catch
Alzheimers? in The Daily Mirror or ?Alzheimers 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
Alzheimers, 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, its 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) Alzheimers
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 Alzheimers 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.
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
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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