Arizona 22 year old diagnosed with Creutzfeldt Jakob Disease CJD
Subject: Arizona 22 year old diagnosed with Creutzfeldt Jakob
Disease CJD
ASU fraternity supports brother facing degenerative brain disease
brandon_londer_for_real Photo by Courtesy of Brittany Londer | The State
Press Brandon Londer, left, poses for a photo with his sister Brittany Londer,
right.
By Alexis Egeland | 11 hours ago Brandon Londer was just another ASU
student: a biomedical engineering senior, a brother of Sigma Alpha Mu
volunteering to help people with disabilities. His whole life changed this past
October, however, when he was diagnosed with Creutzfeldt-Jakob Disease.
Creutzfeldt-Jakob Disease is a degenerative brain disease similar to
Alzheimer's. According to the Alzheimer's Association's website, it causes a
type of dementia that develops unusually fast, much faster than Alzheimer's or
other degenerative diseases.
While Alzheimer's typically takes 20 to 30 years to fully develop,
Creutzfeldt-Jakob Disease only takes a matter of months, and there is no known
cure.
"The best way to describe it is like Alzheimer's on steroids," Brittany
Londer, Brandon's sister, said.
About 300 people are diagnosed with Creutzfeldt-Jakob Disease each year,
and patients are typically aged 60 or older.
Brandon is 22.
Supply chain management sophomore Stephan Plofsky, Brandon's friend and
co-Philanthropy Fundraiser Chairman of Sigma Alpha Mu, said he was surprised by
how fast his condition has developed.
"I visited him in the hospital in November and he was up walking around,
joking with all of us," Plofsky said. "But when I went back in March, just a few
months later, he was practically unresponsive."
Brandon's family has come to Arizona to help him as his condition worsens —
he no longer speaks, rarely moves from the couch and has no recollection of his
friends.
Tourism development and management senior Matt Metviner, Brandon's best
friend, said Brandon was always involved in helping others.
"He was a biomedical engineering major so he didn't have much free time,
but he spent the time he did have helping autistic children or helping design
prosthetic limbs for war veterans," Metviner said. "Brandon was always the first
to help others, so it would be great to see people put him first now."
The 30 active brothers of Sigma Alpha Mu are working to raise money for
Brandon as well.
The fraternity has started a GoFundMe page and is hosting a softball
tournament on April 17, and an on-campus bake sale and raffle on April 10. They
are also hosting a "Percentage Week" at California Pizza Kitchen, where a
portion of all profits will be donated to Brandon's family and to the
Creutzfeldt-Jakob Disease Foundation.
The GoFundMe page has earned $1,704 of its $7,000 goal so far, with just 54
contributions.
Plofsky said many people know about dementia-causing diseases like
Alzheimer's, but very few know about Creutzfeldt-Jakob disease. Because of this,
little money is put into research for the disease. Sigma Alpha Mu's goal is not
only to raise money for Brandon specifically, but to raise awareness about the
disease in general.
"Any donation, even a penny, counts," Metviner said.
All of the money that is raised from the fraternity's events and the
GoFundMe page will be given either to the disease's foundation or to Brandon's
family.
"I just wish people understood how much of a nightmare this is for his
family," Metviner said.
sad face 
2015-2016
***********OCTOBER 2015*************
*** PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS ***
THANK YOU PRION 2015 TAYLOR & FRANCIS, Professor Chernoff, and
Professor Aguzzi et al, for making these PRION 2015 Congressional Poster and
Oral Abstracts available freely to the public. ...Terry S. Singeltary Sr.
O.05: Transmission of prions to primates after extended silent incubation
periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Val erie Durand, Sophie Luccantoni,
Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys
Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies
reputed to be transmissible under field conditions since decades. The
transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that
an animal PD might be zoonotic under appropriate conditions. Contrarily, in the
absence of obvious (epidemiological or experimental) elements supporting a
transmission or genetic predispositions, PD, like the other proteinopathies, are
reputed to occur spontaneously (atpical animal prion strains, sporadic CJD
summing 80% of human prion cases). Non-human primate models provided the first
evidences supporting the transmissibiity of human prion strains and the zoonotic
potential of BSE. Among them, cynomolgus macaques brought major information for
BSE risk assessment for human health (Chen, 2014), according to their
phylogenetic proximity to humans and extended lifetime. We used this model to
assess the zoonotic potential of other animal PD from bovine, ovine and cervid
origins even after very long silent incubation periods. ***We recently observed
the direct transmission of a natural classical scrapie isolate to macaque after
a 10-year silent incubation period, with features similar to some reported for
human cases of sporadic CJD, albeit requiring fourfold longe incubation than
BSE. ***Scrapie, as recently evoked in humanized mice (Cassard, 2014), is the
third potentially zoonotic PD (with BSE and L-type BSE), ***thus questioning the
origin of human sporadic cases. We will present an updated panorama of our
different transmission studies and discuss the implications of such extended
incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases...
===============
***Our study demonstrates susceptibility of adult cattle to oral
transmission of classical BSE. ***
***our findings suggest that possible transmission risk of H-type BSE to
sheep and human. ***
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants
and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and
humans at the molecular level, we investigated the ability of abnormal prion
protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical
scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to
proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding
cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from
transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc
seed from typical and atypical BSE- or typical scrapie-infected brain
homogenates from native host species. In the conventional PMCA, the conversion
of PrPC to PrPres was observed only when the species of PrPC source and PrPSc
seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA
and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested
prion strains. On the other hand, human PrPC was converted by PrPSc from typical
and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports
describing the lack of transmissibility of H-type BSE to ovine and human
transgenic mice, ***our findings suggest that possible transmission risk of
H-type BSE to sheep and human. Bioassay will be required to determine whether
the PMCA products are infectious to these animals.
================
==========================================
***our findings suggest that possible transmission risk of H-type BSE to
sheep and human. Bioassay will be required to determine whether the PMCA
products are infectious to these animals.
==========================================
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Transmission of scrapie prions to primate after an extended silent
incubation period
Authors
item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire,
Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item
Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item
Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron,
Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item
Deslys, Jean-Philippe -
Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015
Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E.,
Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C.,
Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J.
2015. Transmission of scrapie prions to primate after an extended silent
incubation period. Scientific Reports. 5:11573.
Interpretive Summary:
The transmissible spongiform encephalopathies (also called prion diseases)
are fatal neurodegenerative diseases that affect animals and humans. The agent
of prion diseases is a misfolded form of the prion protein that is resistant to
breakdown by the host cells. Since all mammals express prion protein on the
surface of various cells such as neurons, all mammals are, in theory, capable of
replicating prion diseases. One example of a prion disease, bovine spongiform
encephalopathy (BSE; also called mad cow disease), has been shown to infect
cattle, sheep, exotic undulates, cats, non-human primates, and humans when the
new host is exposed to feeds or foods contaminated with the disease agent. The
purpose of this study was to test whether non-human primates (cynomologous
macaque) are susceptible to the agent of sheep scrapie. After an incubation
period of approximately 10 years a macaque developed progressive clinical signs
suggestive of neurologic disease. Upon postmortem examination and microscopic
examination of tissues, there was a widespread distribution of lesions
consistent with a transmissible spongiform encephalopathy. This information will
have a scientific impact since it is the first study that demonstrates the
transmission of scrapie to a non-human primate with a close genetic relationship
to humans. This information is especially useful to regulatory officials and
those involved with risk assessment of the potential transmission of animal
prion diseases to humans.
Technical Abstract:
Classical bovine spongiform encephalopathy (c-BSE) is an animal prion
disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the
past decades, c-BSE's zoonotic potential has been the driving force in
establishing extensive protective measures for animal and human health. In
complement to the recent demonstration that humanized mice are susceptible to
scrapie, we report here the first observation of direct transmission of a
natural classical scrapie isolate to a macaque after a 10-year incubation
period. Neuropathologic examination revealed all of the features of a prion
disease: spongiform change, neuronal loss, and accumulation of PrPres throughout
the CNS.
***This observation strengthens the questioning of the harmlessness of
scrapie to humans, at a time when protective measures for human and animal
health are being dismantled and reduced as c-BSE is considered controlled and
being eradicated. Our results underscore the importance of precautionary and
protective measures and the necessity for long-term experimental transmission
studies to assess the zoonotic potential of other animal prion strains.
***This information will have a scientific impact since it is the first
study that demonstrates the transmission of scrapie to a non-human primate with
a close genetic relationship to humans. This information is especially useful to
regulatory officials and those involved with risk assessment of the potential
transmission of animal prion diseases to humans.
***This observation strengthens the questioning of the harmlessness of
scrapie to humans, at a time when protective measures for human and animal
health are being dismantled and reduced as c-BSE is considered controlled and
being eradicated. Our results underscore the importance of precautionary and
protective measures and the necessity for long-term experimental transmission
studies to assess the zoonotic potential of other animal prion strains.
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS
*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***
O18
Zoonotic Potential of CWD Prions
Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1,
Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve
University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy,
3Encore Health Resources, Houston, Texas, USA
*** These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.
==================
***These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.***
==================
P.105: RT-QuIC models trans-species prion transmission
Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover
Prion Research Center; Colorado State University; Fort Collins, CO USA
Conversely, FSE maintained sufficient BSE characteristics to more
efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was
competent for conversion by CWD and fCWD.
***This insinuates that, at the level of protein:protein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.
================
***This insinuates that, at the level of protein:protein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.***
================
*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***
Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014
*** chronic wasting disease, there was no absolute barrier to conversion of
the human prion protein.
*** Furthermore, the form of human PrPres produced in this in vitro assay
when seeded with CWD, resembles that found in the most common human prion
disease, namely sCJD of the MM1 subtype.
*** These results would seem to suggest that CWD does indeed have zoonotic
potential, at least as judged by the compatibility of CWD prions and their human
PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests
that if zoonotic CWD occurred, it would most likely effect those of the PRNP
codon 129-MM genotype and that the PrPres type would be similar to that found in
the most common subtype of sCJD (MM1).***
*** The potential impact of prion diseases on human health was greatly
magnified by the recognition that interspecies transfer of BSE to humans by beef
ingestion resulted in vCJD. While changes in animal feed constituents and
slaughter practices appear to have curtailed vCJD, there is concern that CWD of
free-ranging deer and elk in the U.S. might also cross the species barrier.
Thus, consuming venison could be a source of human prion disease. Whether BSE
and CWD represent interspecies scrapie transfer or are newly arisen prion
diseases is unknown. Therefore, the possibility of transmission of prion disease
through other food animals cannot be ruled out. There is evidence that vCJD can
be transmitted through blood transfusion. There is likely a pool of unknown size
of asymptomatic individuals infected with vCJD, and there may be asymptomatic
individuals infected with the CWD equivalent. These circumstances represent a
potential threat to blood, blood products, and plasma supplies.
Tuesday, April 12, 2016
The first detection of Chronic Wasting Disease (CWD) in Europe
Sunday, April 10, 2016
Norwegian Veterinary Institute (NVI, 2016) has reported a case of prion
disease Cervid Spongiform Encephalopathy detected in free ranging wild reindeer
(Rangifer tarandus tarandus)
Monday, April 11, 2016
***DECLARATION OF EXTRAORDINARY EMERGENCY DUE TO A FOREIGN ANIMAL DISEASE
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION CHRONIC WASTING DISEASE CWD IN
THE UNITED STATES AND NORTH AMERICA ? ***
MAD SHEEP OF MAD RIVER VALLEY AND THE USDA ‘FALSE FLAG’ WAR ON THAT FAMILY,
AND WHY TODAY A DECLARATION OF EXTRAORDINARY EMERGENCY DUE TO A FOREIGN ANIMAL
DISEASE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION CHRONIC WASTING
DISEASE CWD IN THE UNITED STATES AND NORTH AMERICA MUST BE CALLED FOR !!!
Friday, March 18, 2016 CFSAN
Constituent Update: FDA Announces Final Rule on Bovine Spongiform
Encephalopathy BSE MAD COW TSE PRION Center for Food Safety and Applied
Nutrition - Constituent Update
Friday, February 05, 2016
*** Report of the Committee on Wildlife Diseases FY2015 CWD TSE PRION
Detections in Farmed Cervids and Wild
Saturday, February 6, 2016
*** Secretary's Advisory Committee on Animal Health; Meeting [Docket No.
APHIS-2016-0007] Singeltary Submission
The Pathological Protein:
Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases
Philip Yam
''Answering critics like Terry Singeltary, who feels that the US
undercounts CJD, Schonberger _conceded_ that the current surveillance system has
errors but stated that most of the errors will be confined to the older
population''....end
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.
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?
The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003
doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI
Tracking spongiform encephalopathies in North America
Original
Xavier Bosch
“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 ...
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
Evidence for human transmission of amyloid-β pathology and cerebral amyloid
angiopathy
07 02:27 AM
Terry S. Singeltary Sr. said:
re-Evidence for human transmission of amyloid-β pathology and cerebral
amyloid angiopathy
2015-12-07 02:27 AM
Terry S. Singeltary Sr. said: 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)
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.]
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 ?
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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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
the warning shots fired over the bow of the boat that were never heard ;
PITUITARY EXTRACT
This was used to help cows super ovulate. This tissue was considered to be
of greatest risk of containing BSE and consequently transmitting the disease...
NON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLE
snip...
I was quite prepared to believe in unofficial pituitary hormones, also in
the 1970's, whether as described by Dr. Little, or in other circumstances, for
animal use.
snip...
The fact that there were jars of pituitaries (or extract) around on shelves
is attested by the still potent 1943 pituitaries, described in Stockell Hartree
et al. (J/RF/17/291) which had come from the lab. at Mill Hill. Having taken the
trouble to collect them, they were not lightly thrown out...
3. The extraction is from a pool of pituitary glands collected from
abbatoirs and the process used is unlikely to have any effect on the BSE agent.
Hormones extracted from human pituitary glands have been responsible for a small
number of Creutzfeldt Jacob disease in man.
SEE LOOPHOLE ;
SEE LOOPHOLE SHOULD BE CLOSED ;
snip...see at bottom ;
Thursday, August 13, 2015
Iatrogenic CJD due to pituitary-derived growth hormone with genetically
determined incubation times of up to 40 years
*** PRION2015 Alzheimer’s disease ***
*** P.34: Preliminary study of Alzheimer’s disease transmission to bank
vole
Guido Di Donato1, Geraldina Riccardi1, Claudia D’Agostino1, Flavio
Torriani1, Maurizio Pocchiari2, Romolo Nonno1, Umberto Agrimi1, and Michele
Angelo Di Bari1
1Department of Food Safety and Veterinary Public Health Istituto Superiore
di Sanit a, Rome, Italy; 2Department of Cellular Biology and Neuroscience;
Istituto Superiore di Sanit a, Rome, Italy
Extensive experimental findings indicate that prion-like mechanisms underly
the pathogenesis of Alzheimer disease (AD). Transgenic mice have been pivotal
for investigating prionlike mechanisms in AD, still these models have not been
able so far to recapitulate the complex clinical-pathological features of AD.
Here we aimed at investigating the potential of bank vole, a wild-type rodent
highly susceptible to prions, in reproducing AD pathology upon experimental
inoculation.
Voles were intracerebrally inoculated with brain homogenate from a familial
AD patient. Animals were examined for the appearance of neurological signs until
the end of experiment (800 d post-inoculation, d.p.i.). Brains were studied by
immunohistochemistry for pTau Prion 2015 Poster Abstracts S29 (with AT180 and
PHF-1 antibodies) and b-amyloid (4G8).
Voles didn’t show an overt clinical signs, still most of them (11/16) were
found pTau positive when culled for intercurrent disease or at the end of
experiment. Interestingly, voles culled as early as 125 d.p.i. already showed
pTau aggregates. Deposition of pTau was similar in all voles and was
characterized by neuropil threads and coiled bodies in the alveus, and by rare
neurofibrillary tangles in gray matter. Conversely, b-amyloid deposition was
rather rare (2/16). Nonetheless, a single vole showed the contemporaneous
presence of pTau in the alveus and a few Ab plaque-like deposits in the
subiculum. Uninfected age-matched voles were negative for pTau and Ab.
*** These findings corroborate and extend previous evidences on the
transmissibility of pTau and Ab aggregation. Furthermore, the observation of a
vole with contemporaneous propagation of pTau and Ab is intriguing and deserves
further studies.
=================
P.155: Quantitative real-time analysis of disease specific tau amyloid
seeding activity
Davin Henderson and Edward Hoover Prion Research Center; College of
Veterinary Medicine and Biomedical Sciences; Colorado State University; Fort
Collins, CO USA
A leading hypothesis for the cause of neurodegenerative diseases is the
templated misfolding of cellular proteins to an amyloid state. Spongiform
encephalopathies were the first diseases discovered to be caused by a misfolded
amyloid-rich protein. It is now recognized that the major human
neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s
disease (PD), and chronic traumatic encephalopathy (CTE), also are associated
with amyloid formation. Moreover, AD and PD amyloids have been shown competent
to transmit disease in experimental animal models, suggesting shared mechanisms
with traditional prion diseases. Sensitive detection of prion disease has been
advanced by in vitro amplification of low levels of disease specific amyloid
seeds, e.g. serial protein misfolding amplification (sPMCA), amyloid seeding
(ASA) and real-time quaking induced conversion (RT-QuIC), thereby replicating
the disease process in vitro. In addition, measurement of the amyloid formation
rate can estimate the level of disease-associated seed by using methods
analogous to quantitative polymerase chain reaction (qPCR). In the present work,
we apply these principles to show that seeding activity of in vitro generated
amyloid tau and AD brain amyloid tau can be readily detected and
quantitated.
=============
P.83: Gerstmann-Str€aussler-Scheinker disease with F198S mutation:
Selective propagation of PrPSc and pTau upon inoculation in bank vole
Michele Angelo Di Bari1, Romolo Nonno1, Laura Pirisinu1, Claudia
D’Agostino1, Geraldina Riccardi1, Guido Di Donato1, Paolo Frassanito1,
Bernardino Ghetti2, Pierluigi Gambetti3, and Umberto Agrimi1
1Department of Veterinary Public Health and Food Safety; Istituto Superiore
di Sanit a; Rome, Italy;
2Indiana University-Purdue University Indianapolis; Department of Pathology
and Laboratory Medicine; Indianapolis, IN USA; 3Case Western Reserve University;
Cleveland, OH USA
Gerstmann-Str€aussler-Scheinker disease with F198S mutation (GSS-F198S) is
characterized by the presence of PrP amyloid plaques as well as neurofibrillary
tangles with abnormally-phosphorylated tau protein (pTau) in the brain. The
relationship between tau protein and PrP in the pathogenesis of GSS-F198S is
unknown. In a previous study, we inoculated intracerebrally 2 GSS-F198S cases in
2 lines of voles carrying either methionine (Bv109M) or isoleucine (Bv109I) at
codon 109 of PrP. GSS-F198S transmitted rather efficiently to Bv109I, but not to
Bv109M.
Here we investigated the presence of pTau, as assessed by
immunohistochemistry with anti-pTau antibodies AT180 and PHF-1, in the same
voles previously inoculated with GSSF198S. Among these voles, most Bv109I showed
clinical signs after short survival times (»150 d.p.i.) and were positive for
PrPSc. The remaining Bv109I and all Bv109M survived for longer times without
showing prion-related pathology or detectable PrPSc. All Bv109I which were
previously found PrPSc-positive,
S54 Prion 2015 Poster Abstracts
were immunonegative for pTau deposition. In contrast, pTau deposition was
detected in 16/20 voles culled without clinical signs after long survival times
(225–804 d.p.i.). pTau deposition was characterized by neuropil threads and
coiled bodies in the alveus, and was similar in all voles analyzed.
These findings highlight that pTau from GSS-F198S can propagate in voles.
Importantly, pTau propagation was independent from PrPSc, as pTau was only found
in PrPSc-negative voles surviving longer than 225 d.p.i. Thus, selective
transmission of PrPSc and pTau proteinopathies from GSS-F198S can be
accomplished by experimental transmission in voles.
=========
=========
I3 Aβ Strains and Alzheimer’s Disease
Lary Walker Emory University, Atlanta, GA, USA
An essential early event in the development of Alzheimer’s disease is the
misfolding and aggregation of Aβ. Enigmatically, despite the extensive
deposition of human-sequence Aβ in the aging brain, nonhuman primates do not
develop the full pathologic or cognitive phenotype of Alzheimer’s disease, which
appears to be unique to humans. In addition, some humans with marked Aβ
accumulation in the brain retain their cognitive abilities, raising the question
of whether the pathogenicity of Aβ is linked to the molecular features of the
misfolded protein. I will present evidence for strain-like molecular differences
in aggregated Aβ between humans and nonhuman primates, and among end-stage
Alzheimer patients. I will also discuss a case of Alzheimer’s disease with
atypical Aβ deposition to illustrate heterogeneity in the molecular architecture
of Aβ assemblies, and how this variability might influence the nature of the
disease. As in the case of prion diseases, strain-like variations in the
molecular architecture of Aβ could help to explain the phenotypic variability in
Alzheimer’s disease, as well as the distinctively human susceptibility to the
disorder.
This research was conducted in collaboration with Harry LeVine, Rebecca
Rosen, Amarallys Cintron, David Lynn, Yury Chernoff, Anil Mehta and Mathias
Jucker and colleagues. Supported by AG040589, RR165/OD11132, AG005119, NS077049,
the CART Foundation and MetLife.
==========
I5 Pathogenic properties of synthetically generated prions
Jiyan Ma Van Andel Research Institute, Grand Rapids, Michigan, USA
Synthetically generating prions with bacterially expressed recombinant
prion protein (recPrP) strongly supports the prion hypothesis. Yet, it remains
unclear whether the pathogenic properties of synthetically generated prions
(rec-Prion) fully recapitulate those of naturally occurring prions. A series of
analyses including intracerebral and intraperitoneal transmissions of rec-Prion
in wild-type mice were performed to determine the characteristics of rec-Prion
induced diseases. Results from these analyses demonstrated that the rec-Prion
exhibits the same pathogenic properties with naturally occurring prions,
including a titratable infectivity that can be determined by endpoint titration
assays, capability of transmitting prion disease via routes other than the
direct intra-cerebral inoculation, causing ultra-structural lesions that are
specific to prion disease, and sharing a similar manner of visceral
dissemination and neuroinvasion with naturally occurring scrapie and chronic
wasting disease. These findings confirmed that the disease caused by rec-Prion
in wild-type mice is bona fide prion disease or transmissible spongiform
encephalopathiges, and the rec-Prion contains similar pathogenic properties as
naturally occurring prions.
I6 Transmissible protein toxins in neurodegenerative disease
Jacob Ayers, David Borchelt University of Florida, Gainesville, FL,
USA
Amyotrophic lateral sclerosis (ALS) is an obvious example of
neurodegenerative disease that seems to spread along anatomical pathways. The
spread of symptoms from the site of onset (e.g. limb) to the respiratory
musculature drives the rate of disease progression. In cognitive disorders, such
as Alzheimer’s disease, one can find similarly find evidence of spreading
dysfunction and pathology. One mechanism to account for this spread of disease
from one neural structure to another is by evoking prion-like propagation of a
toxic misfolded protein from cell to cell. Recent studies in animals that model
aspects of Alzheimer’s Disease, Parkinson’s Disease, and Tauopathy, have
bolstered the arguments in favor of prion-like, although in most of these models
the mice do not develop overt “clinical” symptoms. Recently, Jacob Ayers
demonstrated that the symptoms of ALS can be transmitted from a strain of mice
that expresses mutant SOD1-G93A at high levels to a second transgenic strain
that expresses mutant SOD1 at low, nontoxic, levels. This model showed many
prion-like features including evidence of host-adaptation (earlier and more
penetrant disease upon second passage). Interestingly, homogenates from
paralyzed mice expressing the G37R variant of SOD1 transmitted poorly, a finding
suggestive that different SOD1 variants may exhibit strain-like properties.
These “ i n d u c i b l e ” m o d e l s o f h u m a n neurodegenerative disease
enable the generation of models that do not require extraordinary levels of
transgene expression and provide a more precise means of initiating the disease
process, advances that may translate into more predictive pre-clinical
models.
=======
P188 Transmission of amyloid pathology by peripheral administration of
misfolded Aβ
Javiera Bravo-Alegria1 ,2, Rodrigo Morales2, Claudia Duran-Aniotz3, Claudio
Soto2 1University of Los Andes, Santiago, Chile, 2Mitchell Center for
Alzheimer’s Disease and Related Brain Disorders, Department of Neurology,
University of Texas Medical School, Houston, Texas, USA, 3University of Chile,
Santiago, Chile
Misfolding and aggregation of Amyloid-β (Aβ) is one of the primary events
involved in the pathogenesis of Alzheimer's disease (AD). Recently, it has been
proposed that Aβ aggregates can transmit and spread the pathology following a
prion-like mechanism. Prions can be exogenously transmitted by many different
routes of administration. In the case of Aβ, previous studies showed that
intraperitoneal (i.p.) injection of seeds can accelerate cerebral amyloidosis in
mouse models. However, other potential routes have not yet been studied. The
goal of this work was to assess whether Aβ amyloidosis can be seeded in the
brain of a transgenic mouse model of AD by peripheral administration of
misfolded particles.
Young tg2576 animals (50 days old) were inoculated with a pool of brain
extract coming from old Tg2576 animals (10%w/v) by different routes: i.p.
(100μL), eye drops (5μL each eye, 3 times), intramuscular (i.m., 50μL), and per
os (p.o., 1000μL). Animals were sacrificed at 300 days old, and brain samples
were analyzed for amyloid pathology by IHC and ELISA.
The i.p., i.m., and eye drops administration of Aβ seeds significantly
accelerated pathological features in tg2576. Regardless of the higher volume
administered, p.o. treated animals did not show any pathological changes when
compared to untreated controls. Differences in the proportion of diffuse, core
and vascular deposition was observed within experimental groups. Our data show
that peripheral administration of Aβ seeds could accelerate pathological changes
in the brain and suggest that an orchestrated cross-talk between the brain and
peripheral tissues occurs in AD.
==========
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY PRION
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
11:20 AM
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