What if Alzheimer's is caused by an infectious agent? By Roberta B.
Ness
July 30, 2016 Updated: July 31, 2016 5:10pm
What if Alzheimer's is caused by an infectious agent? About 18 months ago,
my father died from complications of Alzheimer's disease. At age 12 he fled the
Nazis with not a nickel in his pocket; at age 55, he was second in command at
the Internal Revenue Service. By the end, his life had narrowed to a day-long
plea to brush his teeth and go to bed.
Just months after his death, still grief-stricken, I gave a TED talk in
Palm Springs about barriers to American innovation. "I kept thinking," I said,
"I am a physician and scientist and I failed him. I cannot - we should not -
accept science's impotence to solve [the cause of] Alzheimer's disease."
Now a radically new possible explanation for the cause of Alzheimer's
disease has emerged - but I'll bet you'll find it less than reassuring.
What if Alzheimer's is caused by an infectious agent? What if that agent
could be transmitted to your brain from another person through brain surgery or
perhaps could even be transmitted to your brain by eating tainted meat. Could
such nightmare scenarios be possible?
To explain, let's turn back the clock to 1982. Stanley Prusiner, now at the
University of California, San Francisco, proposed a radical explanation for the
cause of a family of strange neurologic disorders that could be transmitted to
mice or monkeys via injection of diseased brain tissue. Despite an exhaustive
search, scientists had been unable to find in the diseased brains any foreign
DNA or RNA representing an infection. Prusiner proposed a crazy idea (at least
it seemed so at the time): "prions."
What if Alzheimer's is caused by an infectious agent?
Prions are a class of proteins that exist in a normal cellular form but
also can become misfolded. The misfolded form has only to touch the normal
protein and it too misfolds, creating a cascade that turns brain cells into a
spongy mess.
Creutzfeldt–Jakob disease (CJD) is a prion disease that affected an
unfortunate group of children who, years ago got a contaminated batch ofhuman
growth hormone. Mad cow disease - the technical term is bovine spongiform
encephalopathy - is another prion disease that may sound more familiar. It has
sickened and killed over 200 people who ate infected cattle in the early 1990s.
Fortunately, new infections have been eliminated in the U.S. - as far as public
health agencies know - by banning the feeding of meat and bone meal to cattle,
import controls and the discarding by U.S. slaughterhouses of neurologic tissue
from cattle.
Alzheimer's disease also has recently been recognized as a prion-associated
disease. The hallmark pathology seen in the brains of people with Alzheimer's,
amyloid-β and tau, turn out to also be misfolded proteins. But data showing that
amyloid and tau might be contagious have been absent - until now.
What has been known for almost a decade is that injection of amyloid-β into
mice seeds an abnormal build-up of amyloid in mice brains. Amyloid spreads from
cell to cell within the brain. Mice, of course, are not human and so although
this research has been accepted with interest, it has not raised any
alarms.
Then last year, British researchers reported that the brains of patients
who died from CJD (as a result of injections from the tainted growth hormone)
contained an abnormally large number of amyloid deposits. The worrying
conclusion from these observations: that the hormone injections might have
transmitted prions causing CJD but also causing the build-up of amyloid and thus
Alzheimer's. Amyloid build-up is known to proceed the symptoms of Alzheimer's by
several decades, so the fateful growth hormone injections, which occurred in the
1960s-'80s might be showing up only recently.
You can just imagine how controversial all of this is, so don't take any of
this as gospel. But if it is true, what makes it scary is that prions are
terribly hardy. The normal procedures historically used to sterilize instruments
used in brain surgery do not always destroy them. Equipment from brain surgery
conducted on a patient with CJD or with Alzheimer's might at least
hypothetically cause a subsequent patient to develop Alzheimer's 30 or 40 years
down the road. Eating meat from cows with undetected mad cow disease, too, might
hypothetically cause later Alzheimer's disease. No one knows if any of these
speculative scenarios could occur.
The good news is that mad cow seems to have been eliminated from
U.S.-supplied beef. Moreover, now that the possibility of contagion by brain
surgery has arisen, scientists are scrambling to find out if there is any such
risk and, if so, how to eliminate it. No one wants to consider the specter of
having been accidentally infected decades ago - and thus being at risk for
developing Alzheimer's disease in the future. But if such things happened in the
past, at least that knowledge will allow us to find ways to prevent such a cause
for Alzheimer's in our children.
I have been asking this very same question for 15 plus years...trying to
bring this to the attention to someone that would investigate this with great
urgency...I believe the elephant in the room with Alzheimer’s disease that
everyone has ignored is the TSE Prion iatrogenic potential...
SWISS MEDICAL WEEKLY
Alzheimer-type brain pathology may be transmitted by grafts of dura mater 26/01/2016 Singeltary comment ;
http://blog.smw.ch/alzheimer-type-brain-pathology-may-be-transmitted-by-grafts-of-dura-mater/#comment-89016
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.
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
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 ;
2012 Singeltary on CJD and Alzheimer’s and iatrogenic threat
Proposal ID: 29403
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Background
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease
have both been around a long time, and was discovered in or around the same time
frame, early 1900’s. Both disease, and it’s variants, in many cases are merely
names of the people that first discovered them. Both diseases are incurable and
debilitating brain disease, that are in the end, 100% fatal, with the
incubation/clinical period of the Alzheimer’s disease being longer than the TSE
prion disease. Symptoms are very similar, and pathology is very similar. I
propose that Alzheimer’s is a TSE disease of low dose, slow, and long incubation
disease, and that Alzheimer’s is Transmissible, and is a threat to the public
via the many Iatrogenic routes and sources. It was said long ago that the only
thing that disputes this, is Alzheimer’s disease transmissibility, or the lack
of. today, there is enough documented science (some confidential), that shows
that indeed Alzheimer’s is transmissible. The risk factor for friendly fire, and
or the pass-it-forward mode i.e. Iatrogenic transmission is a real threat, and
one that needs to be addressed immediately.
Methods
Through years of research, as a layperson, of peer review journals,
transmission studies, and observations of loved ones and friends that have died
from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant
Creutzfelt Jakob Disease CJD.
Results
The likelihood of many victims of Alzheimer’s disease from the many
different Iatrogenic routes and modes of transmission as with the TSE prion
disease. TSE prion disease survives ashing to 600 degrees celsius, that’s around
1112 degrees farenheit. you cannot cook the TSE prion disease out of meat. you
can take the ash and mix it with saline and inject that ash into a mouse, and
the mouse will go down with TSE. Prion Infected Meat-and-Bone Meal Is Still
Infectious after Biodiesel Production as well. the TSE prion agent also survives
Simulated Wastewater Treatment Processes. IN fact, you should also know that the
TSE Prion agent will survive in the environment for years, if not decades. you
can bury it and it will not go away. TSE prion agent is capable of infected your
water table i.e. Detection of protease-resistant cervid prion protein in water
from a CWD-endemic area. it’s not your ordinary pathogen you can just cook it
out and be done with. that’s what’s so worrisome about Iatrogenic mode of
transmission, a simple autoclave will not kill this TSE prion agent.
Conclusions
There should be a Global Congressional Science round table event (one of
scientist and doctors et al only, NO CORPORATE, POLITICIANS ALLOWED) set up
immediately to address these concerns from the many potential routes and sources
of the TSE prion disease, including Alzheimer’s disease, and a emergency global
doctrine put into effect to help combat the spread of Alzheimer’s disease via
the medical, surgical, dental, tissue, and blood arena’s. All human and animal
TSE prion disease, including Alzheimer’s should be made reportable in every
state, and Internationally, WITH NO age restrictions. Until a proven method of
decontamination and autoclaving is proven, and put forth in use universally, in
all hospitals and medical, surgical arena’s, or the TSE prion agent will
continue to spread. IF we wait until science and corporate politicians wait
until politics let science _prove_ this once and for all, and set forth
regulations there from, we will all be exposed to the TSE Prion agents, if that
has not happened already. what’s the use of science progressing human life to
the century mark, if your brain does not work?
combined cannot exceed 350 Words
shortened to proper word count ;
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Background
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease
have both been around a long time, and was discovered in or around the same time
frame, early 1900’s. Both diseases are incurable and debilitating brain disease,
that are in the end, 100% fatal, with the incubation/clinical period of the
Alzheimer’s disease being longer (most of the time) than the TSE prion disease.
Symptoms are very similar, and pathology is very similar.
Methods
Through years of research, as a layperson, of peer review journals,
transmission studies, and observations of loved ones and friends that have died
from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant
Creutzfelt Jakob Disease CJD.
Results
I propose that Alzheimer’s is a TSE disease of low dose, slow, and long
incubation disease, and that Alzheimer’s is Transmissible, and is a threat to
the public via the many Iatrogenic routes and sources. It was said long ago that
the only thing that disputes this, is Alzheimer’s disease transmissibility, or
the lack of. The likelihood of many victims of Alzheimer’s disease from the many
different Iatrogenic routes and modes of transmission as with the TSE prion
disease.
Conclusions
There should be a Global Congressional Science round table event set up
immediately to address these concerns from the many potential routes and sources
of the TSE prion disease, including Alzheimer’s disease, and a emergency global
doctrine put into effect to help combat the spread of Alzheimer’s disease via
the medical, surgical, dental, tissue, and blood arena’s. All human and animal
TSE prion disease, including Alzheimer’s should be made reportable in every
state, and Internationally, WITH NO age restrictions. Until a proven method of
decontamination and autoclaving is proven, and put forth in use universally, in
all hospitals and medical, surgical arena’s, or the TSE prion agent will
continue to spread. IF we wait until science and corporate politicians wait
until politics lets science _prove_ this once and for all, and set forth
regulations there from, we will all be exposed to the TSE Prion agents, if that
has not happened already.
end...tss
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
source references ...end...tss
Hello Nicole,
by all means, please do use my poster. but I thought this was already
taken care of, and I could not attend for my poster presentation, therefore, it
was not going to be presented. I have some health issues and could not make the
trip.
please see old correspondence below...
From: Nicole Sanders Sent: Tuesday, April 10, 2012 5:37 PM To: Terry S.
Singeltary Sr. Subject: RE: re-submission
Dear Terry,
The decline of proposal number 30756 is registered in the system. Thank
you for your consideration.
Best Regards,
Nicole
Nicole Sanders
Senior Specialist, Membership & Conference Programming
______________________________________
Alzheimer’s Association – National Office
225 North Michigan Avenue – Floor 17
Chicago, Illinois 60601
Office: 312-335-5897| Fax: 866-560-0650 | Email: nicole.sanders@alz.org
From: Terry S. Singeltary Sr. [mailto:flounder9@verizon.net] Sent:
Saturday, April 07, 2012 9:47 PM To: Nicole Sanders Subject: Re: re-submission
Greetings, Alzheimer’s Association and Ms Nicole Sanders,
Thank You for accepting my submission # 29403, Alzheimer’s disease and
Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ? and
the opportunity to present it, at the Alzheimer’s Association International
Conference 2012 (AAIC), as a poster presentation. However, with great sadness, I
must regretfully decline the invitation due to a medical reasons, and traveling
to Canada, of which is not possible. ...
Thank You,
With Kindest Regards,
I am sincerely,
Terry S. Singeltary Sr.
xxx
Bacliff, Texas USA 77518
flounder9@verizon.net
From: Nicole Sanders
Sent: Saturday, April 07, 2012 8:20 PM
To: Terry S. Singeltary Sr.
Subject: RE: re-submission
Dear Terry,
*** Yes, your proposal was accepted as a poster presentation. Please
decline the invitation if appropriate.
Best Regards,
Nicole
Nicole Sanders
Senior Specialist, Membership & Conference Programming
______________________________________
Alzheimer’s Association – National Office
225 North Michigan Avenue – Floor 17
Chicago, Illinois 60601
Office: 312-335-5897| Fax: 866-560-0650 | Email: nicole.sanders@alz.org
From: Terry S. Singeltary Sr. [mailto:flounder9@verizon.net] Sent:
Tuesday, April 03, 2012 10:06 AM To: Nicole Sanders Subject: re-submission
Hi Ms Sanders Ma’am,
I am a bit confused as to the format this was accepted.
do I have to attend for this to be presented as a poster. I am disabled
and cannot attend. I hope this is not the case.
Thanks !
kind regards,
terry
From: Nicole.sanders@alz.org
Sent: Tuesday, April 03, 2012 9:26 AM
To: flounder9@verizon.net
Subject: 2012 AAIC Oral Abstract Notification
Dear Terry S. Singeltary:
We regret to inform you that your abstract entitled, "Alzheimer’s disease
and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if
?," has not been accepted for an oral presentation but I am pleased to inform
you that your abstract submission has been accepted for a poster presentation at
the Alzheimer’s Association International Conference(AAIC) 2012 in Vancouver,
British Columbia, Canada, July 14-19, 2012.
Please refer to the presentation format below and confirm your intent to
present by Friday, April 6, 2012 by selecting “Confirm” or “Decline” within this
message. Once you have made your selection, you will be unable to makes changes.
Please contact Nicole Sanders mailto:nicole.sanders@alz.org for assistance. If
you do not reply by Friday April 6, your abstract will be removed from the
program.
Click Here to Accept http://www.softconference.com/Subs/icad/2012/ICAD_Accept_Decline_Poster.asp?FacID=129919&PID=70543&Status=1
Click Here to Decline http://www.softconference.com/Subs/icad/2012/ICAD_Accept_Decline_Poster.asp?FacID=129919&PID=70543&Status=2
Session/Presentation Details Poster Date:Jul 17, 2012 *Please use the
Proposal Number in all correspondence regarding your presentation.
Presentation Format Poster presentations are numbered and grouped by
overall topic category. 500 posters will be displayed each day in the Exhibit
Hall.
=======================================================
From: Nicole Sanders Sent: Friday, May 04, 2012 6:10 PM To:
flounder9@verizon.net Subject: Urgent Request- Response Required- AAIC 2012
Poster Presentation
Dear Terry Singeltary:
The Scientific Program Committee, has accepted your proposal for a poster
presentation at the Alzheimer’s Association International Conference in
Vancouver, British Columbia, Canada, July 14 - 19, 2012. However we have not
received your response.
Please refer to the presentation format below and confirm your intent to
present by Wednesday, May 9, 2012 by responding to this e-mail. If we do not
receive a response by May 9 your presentation will be removed from the program.
Session/Presentation Detail Proposal Number*: 29403
Presentation Title: Alzheimer’s disease and Transmissible Spongiform
Encephalopathy prion disease, Iatrogenic, what if ? Session Type: Poster Session
Title: 2012 Tuesday Posters Session Date and Time: Tuesday, July 17 1 – 3 p.m.
Presentation Number: P3-151
*Please use Proposal Number in all correspondence regarding your
presentation.
Presentation Format The Oral Presentation is a 90-minute session, grouped
by overall category topic, which will begin with introductions by the session
chair. There will be seven concurrent oral presentation sessions with six
speakers per session. Each speaker will have approximately 12 minutes for
presentation, followed by a three-minute questions-and-answer period. The
session location can be found in the on-site program book and or on the
conference web site beginning in June.
Best Regards,
Nicole
Nicole Sanders Senior Specialist, Membership & Conference
Programming Alzheimer's Association nicole.sanders@alz.org
end...tss
Thursday, August 13, 2015
Iatrogenic CJD due to pituitary-derived growth hormone with genetically
determined incubation times of up to 40 years
http://creutzfeldt-jakob-disease.blogspot.com/2015/08/iatrogenic-cjd-due-to-pituitary-derived.html
http://creutzfeldt-jakob-disease.blogspot.com/2015/08/iatrogenic-cjd-due-to-pituitary-derived.html
*** 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.
==========
Invited Review
Prion-like transmission and spreading of tau pathology
Florence Clavaguera1, Jürgen Hench1, Michel Goedert2 and Markus Tolnay1,*
DOI: 10.1111/nan.12197
This article is protected by copyright. All rights reserved.
Additional Information(Hide All) Author InformationPublication History
Author Information 1 Institute of Pathology, University Hospital Basel,
Schönbeinstrasse 40, CH-4031 Basel, Switzerland 2 MRC Laboratory of Molecular
Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK * Please send
correspondence to Markus Tolnay at the above address. Email:
markus.tolnay@usb.ch
This article has been accepted for publication and undergone full peer
review but has not been through the copyediting, typesetting, pagination and
proofreading process, which may lead to differences between this version and the
Version of Record. Please cite this article as doi: 10.1111/nan.12197
Publication History Accepted manuscript online: 17 NOV 2014 01:23AM EST
Manuscript Accepted: 13 NOV 2014
Abstract
Filaments made of hyperphosphorylated tau protein are encountered in a
number of neurodegenerative diseases referred to as “tauopathies”. In the most
prevalent tauopathy, Alzheimer's disease, tau pathology progresses in a
stereotypical manner with the first lesions appearing in the locus coeruleus and
the entorhinal cortex from where they appear to spread to the hippocampus and
neocortex. Propagation of tau pathology is also characteristic of argyrophilic
grain disease, where the tau lesions appear to spread throughout distinct
regions of the limbic system. These findings strongly implicate neuron-to-neuron
propagation of tau aggregates. Isoform composition and morphology of tau
filaments can differ between tauopathies suggesting the existence of
conformationally diverse tau strains. ***Altogether, this points to prion-like
mechanisms in the pathogenesis of tauopathies.
Wednesday, June 19, 2013
Spreading of tau pathology in Alzheimer's disease by cell-to-cell
transmission Spreading of tau pathology in Alzheimer's disease by cell-to-cell
transmission
Nguyen-Vi Mohamed, Thibaut Herrou, Vanessa Plouffe, Nicolas Piperno, Nicole
Leclerc*
Article first published online: 16 JUN 2013
DOI: 10.1111/ejn.12229
© 2013 Federation of European Neuroscience Societies and John Wiley &
Sons Ltd
Keywords:
Alzheimer's disease; endocytosis and secretion; propagation; tau
Abstract
It is well documented that neurofibrillary tangles composed of aggregated
tau protein propagate in a predictable pattern in Alzheimer's disease (AD). The
mechanisms underlying the propagation of tau pathology are still poorly
understood. Recent studies have provided solid data demonstrating that in
several neurodegenerative diseases including AD, the spreading of misfolded
protein aggregates in the brain would result from prion-like cell-to-cell
transmission. Consistent with this new concept, recent studies have reported
that human tau can be released in the extracellular space by an active process
of secretion, and can be endocytosed both in vitro and in vivo. Most
importantly, it was reported that the spreading of tau pathology was observed
along synaptically connected circuits in a transgenic mouse model where human
tau overexpression was restricted in the entorhinal cortex. This indicates that
secretion of tau by presynaptic neurons and its uptake by postsynaptic neurons
could be the sequential events leading to the propagation of tau pathology in
the brain.
Published online before print May 20, 2013, doi: 10.1073/pnas.1301175110
PNAS May 20, 2013
Brain homogenates from human tauopathies induce tau inclusions in mouse
brain
Florence Clavagueraa, Hiroyasu Akatsub, Graham Fraserc, R. Anthony
Crowtherc, Stephan Franka, Jürgen Hencha, Alphonse Probsta, David T. Winklera,d,
Julia Reichwalde, Matthias Staufenbiele, Bernardino Ghettif, Michel
Goedertc,1,2, and Markus Tolnaya,1,2
aDepartment of Neuropathology, Institute of Pathology, University Hospital,
4031 Basel, Switzerland; bChoju Medical Institute, Fukushimura Hospital,
Toyohashi City 441-8124, Japan; cMedical Research Council Laboratory of
Molecular Biology, Cambridge CB2 0QH, United Kingdom; dDepartment of Neurology,
University Hospital, 4031 Basel, Switzerland; eNovartis Institutes for
Biomedical Research, 4056 Basel, Switzerland; and fIndiana Alzheimer Disease
Center and Department of Pathology and Laboratory Medicine, Indiana University,
Indianapolis, IN 46202
Edited by Anders Bjorklund, Lund University, Lund, Sweden, and approved
April 25, 2013 (received for review January 18, 2013)
Filamentous inclusions made of hyperphosphorylated tau are characteristic
of numerous human neurodegenerative diseases, including Alzheimer’s disease,
tangle-only dementia, Pick disease, argyrophilic grain disease (AGD),
progressive supranuclear palsy, and corticobasal degeneration. In Alzheimer’s
disease and AGD, it has been shown that filamentous tau appears to spread in a
stereotypic manner as the disease progresses. We previously demonstrated that
the injection of brain extracts from human mutant P301S tau-expressing
transgenic mice into the brains of mice transgenic for wild-type human tau (line
ALZ17) resulted in the assembly of wild-type human tau into filaments and the
spreading of tau inclusions from the injection sites to anatomically connected
brain regions. Here we injected brain extracts from humans who had died with
various tauopathies into the hippocampus and cerebral cortex of ALZ17 mice.
Argyrophilic tau inclusions formed in all cases and following the injection of
the corresponding brain extracts, we recapitulated the hallmark lesions of AGD,
PSP and CBD. Similar inclusions also formed after intracerebral injection of
brain homogenates from human tauopathies into nontransgenic mice. Moreover, the
induced formation of tau aggregates could be propagated between mouse brains.
These findings suggest that once tau aggregates have formed in discrete brain
areas, they become self-propagating and spread in a prion-like manner.
snip...
The present work indicates that once small numbers of tau inclusions have
formed in the brain, they may become selfpropagating and spread in a prion-like
manner, independently of other pathogenic mechanisms. What is true of aggregated
human tau may also be the case of other aggregation-prone proteins that cause
human neurodegenerative diseases, including α-synuclein, superoxide dismutase 1,
huntingtin, trans-activator regulatory (TAR) DNA-binding protein 43 (TDP-43),
and Aβ (47). The inhibition of cell-to-cell transmission of pathological
aggregates, for instance by passive immunotherapy, may constitute an effective
mechanism-based therapeutic strategy for most human neurodegenerative diseases.
*** Infectious agent of sheep scrapie may persist in the environment for at
least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
New studies on the heat resistance of hamster-adapted scrapie agent:
Threshold survival after ashing at 600°C suggests an inorganic template of
replication
The infectious agents responsible for transmissible spongiform
encephalopathy (TSE) are notoriously resistant to most physical and chemical
methods used for inactivating pathogens, including heat. It has long been
recognized, for example, that boiling is ineffective and that higher
temperatures are most efficient when combined with steam under pressure (i.e.,
autoclaving). As a means of decontamination, dry heat is used only at the
extremely high temperatures achieved during incineration, usually in excess of
600°C. It has been assumed, without proof, that incineration totally inactivates
the agents of TSE, whether of human or animal origin.
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel
Production
Histochemical analysis of hamster brains inoculated with the solid residue
showed typical spongiform degeneration and vacuolation. Re-inoculation of these
brains into a new cohort of hamsters led to onset of clinical scrapie symptoms
within 75 days, suggesting that the specific infectivity of the prion protein
was not changed during the biodiesel process. The biodiesel reaction cannot be
considered a viable prion decontamination method for MBM, although we observed
increased survival time of hamsters and reduced infectivity greater than 6 log
orders in the solid MBM residue. Furthermore, results from our study compare for
the first time prion detection by Western Blot versus an infectivity bioassay
for analysis of biodiesel reaction products. We could show that biochemical
analysis alone is insufficient for detection of prion infectivity after a
biodiesel process.
Detection of protease-resistant cervid prion protein in water from a
CWD-endemic area
The data presented here demonstrate that sPMCA can detect low levels of
PrPCWD in the environment, corroborate previous biological and experimental data
suggesting long term persistence of prions in the environment2,3 and imply that
PrPCWD accumulation over time may contribute to transmission of CWD in areas
where it has been endemic for decades. This work demonstrates the utility of
sPMCA to evaluate other environmental water sources for PrPCWD, including
smaller bodies of water such as vernal pools and wallows, where large numbers of
cervids congregate and into which prions from infected animals may be shed and
concentrated to infectious levels.
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
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep
infected with scrapie?
28 Mar 01
Most doctors believe that sCJD is caused by a prion protein deforming by
chance into a killer. But Singeltary thinks otherwise. He is one of a number of
campaigners who say that some sCJD, like the variant CJD related to BSE, is
caused by eating meat from infected animals. Their suspicions have focused on
sheep carrying scrapie, a BSE-like disease that is widespread in flocks across
Europe and North America. Now scientists in France have stumbled across new
evidence that adds weight to the campaigners' fears. To their complete surprise,
the researchers found that one strain of scrapie causes the same brain damage in
mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb...
Tuesday, December 16, 2014
Evidence for zoonotic potential of ovine scrapie prions
Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves
Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle
Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia
Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier
Andréoletti1, Affiliations Contributions Corresponding author Journal name:
Nature Communications Volume: 5, Article number: 5821 DOI:
doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014
Published 16 December 2014 Article tools Citation Reprints Rights &
permissions Article metrics
Abstract
Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant
Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie
prions remains unknown. Mice genetically engineered to overexpress the human
prion protein (tgHu) have emerged as highly relevant models for gauging the
capacity of prions to transmit to humans. These models can propagate human
prions without any apparent transmission barrier and have been used used to
confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie
prions transmit to several tgHu mice models with an efficiency comparable to
that of cattle BSE. The serial transmission of different scrapie isolates in
these mice led to the propagation of prions that are phenotypically identical to
those causing sporadic CJD (sCJD) in humans. These results demonstrate that
scrapie prions have a zoonotic potential and raise new questions about the
possible link between animal and human prions.
Subject terms: Biological sciences• Medical research At a glance
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely
create alarm in some circles even if the result could not be interpreted for
man. I have a view that all these agents could be transmitted provided a large
enough dose by appropriate routes was given and the animals kept long enough.
Until the mechanisms of the species barrier are more clearly understood it might
be best to retain that hypothesis.
snip...
R. BRADLEY
*** 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.
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a.
Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos,
Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT.
Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas.
France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated
bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD)
disease in human. To date, BSE agent is the only recognized zoonotic prion.
Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that
have been circulating for centuries in farmed ruminants there is no apparent
epidemiological link between exposure to ruminant products and the occurrence of
other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD).
However, the zoonotic potential of the diversity of circulating TSE agents has
never been systematically assessed. The major issue in experimental assessment
of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the
biological phenomenon that limits TSE agents’ propagation from a species to
another. In the last decade, mice genetically engineered to express normal forms
of the human prion protein has proved essential in studying human prions
pathogenesis and modeling the capacity of TSEs to cross the human species
barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants,
we study their transmission ability in transgenic mice expressing human PrPC
(HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC
(129Met or 129Val) are used to determine the role of the Met129Val dimorphism in
susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to
propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be
susceptible to BSE in sheep or goat to a greater degree than the BSE agent in
cattle and that these agents can convey molecular properties and
neuropathological indistinguishable from vCJD. However homozygous 129V mice are
resistant to all tested BSE derived prions independently of the originating
species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in
HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the
efficiency of transmission at primary passage was low, subsequent passages
resulted in a highly virulent prion disease in both Met129 and Val129 mice.
Transmission of the different scrapie isolates in these mice leads to the
emergence of prion strain phenotypes that showed similar characteristics to
those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie
prions have a zoonotic potential and raise new questions about the possible link
between animal and human prions.
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.
2016
CHRONIC WASTING DISEASE TSE PRION ZOONOSIS
PRION 2016 TOKYO
Zoonotic Potential of CWD Prions: An Update
Ignazio Cali1, Liuting Qing1, Jue Yuan1, Shenghai Huang2, Diane Kofskey1,3,
Nicholas Maurer1, Debbie McKenzie4, Jiri Safar1,3,5, Wenquan Zou1,3,5,6,
Pierluigi Gambetti1, Qingzhong Kong1,5,6
1Department of Pathology, 3National Prion Disease Pathology Surveillance
Center, 5Department of Neurology, 6National Center for Regenerative Medicine,
Case Western Reserve University, Cleveland, OH 44106, USA.
4Department of Biological Sciences and Center for Prions and Protein
Folding Diseases, University of Alberta, Edmonton, Alberta, Canada,
2Encore Health Resources, 1331 Lamar St, Houston, TX 77010
Chronic wasting disease (CWD) is a widespread and highly transmissible
prion disease in free-ranging and captive cervid species in North America. The
zoonotic potential of CWD prions is a serious public health concern, but the
susceptibility of human CNS and peripheral organs to CWD prions remains largely
unresolved. We reported earlier that peripheral and CNS infections were detected
in transgenic mice expressing human PrP129M or PrP129V. Here we will present an
update on this project, including evidence for strain dependence and influence
of cervid PrP polymorphisms on CWD zoonosis as well as the characteristics of
experimental human CWD prions.
PRION 2016 TOKYO
In Conjunction with Asia Pacific Prion Symposium 2016
PRION 2016 Tokyo
Prion 2016
Prion 2016
Purchase options Price * Issue Purchase USD 198.00
Cervid to human prion transmission
Kong, Qingzhong
Case Western Reserve University, Cleveland, OH, United States
Abstract
Prion disease is transmissible and invariably fatal. Chronic wasting
disease (CWD) is the prion disease affecting deer, elk and moose, and it is a
widespread and expanding epidemic affecting 22 US States and 2 Canadian
provinces so far. CWD poses the most serious zoonotic prion transmission risks
in North America because of huge venison consumption (>6 million deer/elk
hunted and consumed annually in the USA alone), significant prion infectivity in
muscles and other tissues/fluids from CWD-affected cervids, and usually high
levels of individual exposure to CWD resulting from consumption of the affected
animal among often just family and friends. However, we still do not know
whether CWD prions can infect humans in the brain or peripheral tissues or
whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no
essays to reliably detect CWD infection in humans. We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in the
brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the cervid
prion strain and influenced by the host (human) prion protein (PrP) primary
sequence;
(3) Reliable essays can be established to detect CWD infection in
humans;and
(4) CWD transmission to humans has already occurred. We will test these
hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in
vitro approaches.
Aim 1 will prove that the classical CWD strain may infect humans in brain
or peripheral lymphoid tissues at low levels by conducting systemic bioassays in
a set of "humanized" Tg mouse lines expressing common human PrP variants using a
number of CWD isolates at varying doses and routes. Experimental "human CWD"
samples will also be generated for Aim 3.
Aim 2 will test the hypothesis that the cervid-to-human prion transmission
barrier is dependent on prion strain and influenced by the host (human) PrP
sequence by examining and comparing the transmission efficiency and phenotypes
of several atypical/unusual CWD isolates/strains as well as a few prion strains
from other species that have adapted to cervid PrP sequence, utilizing the same
panel of humanized Tg mouse lines as in Aim 1.
Aim 3 will establish reliable essays for detection and surveillance of CWD
infection in humans by examining in details the clinical, pathological,
biochemical and in vitro seeding properties of existing and future experimental
"human CWD" samples generated from Aims 1-2 and compare them with those of
common sporadic human Creutzfeldt-Jakob disease (sCJD) prions.
Aim 4 will attempt to detect clinical CWD-affected human cases by examining
a significant number of brain samples from prion-affected human subjects in the
USA and Canada who have consumed venison from CWD-endemic areas utilizing the
criteria and essays established in Aim 3. The findings from this proposal will
greatly advance our understandings on the potential and characteristics of
cervid prion transmission in humans, establish reliable essays for CWD zoonosis
and potentially discover the first case(s) of CWD infection in humans.
Public Health Relevance There are significant and increasing human exposure
to cervid prions because chronic wasting disease (CWD, a widespread and highly
infectious prion disease among deer and elk in North America) continues
spreading and consumption of venison remains popular, but our understanding on
cervid-to-human prion transmission is still very limited, raising public health
concerns. This proposal aims to define the zoonotic risks of cervid prions and
set up and apply essays to detect CWD zoonosis using mouse models and in vitro
methods. The findings will greatly expand our knowledge on the potentials and
characteristics of cervid prion transmission in humans, establish reliable
essays for such infections and may discover the first case(s) of CWD infection
in humans.
Funding Agency Agency National Institute of Health (NIH)
Institute National Institute of Neurological Disorders and Stroke (NINDS)
Type Research Project (R01)
Project # 1R01NS088604-01A1
Application # 9037884
Study Section Cellular and Molecular Biology of Neurodegeneration Study
Section (CMND)
Program Officer Wong, May
Project Start 2015-09-30
Project End 2019-07-31
Budget Start 2015-09-30
Budget End 2016-07-31
Support Year 1
Fiscal Year 2015
Total Cost $337,507
Indirect Cost $118,756
Institution
Name Case Western Reserve University
Department Pathology
Type Schools of Medicine
DUNS # 077758407
City Cleveland
State OH
Country United States
Zip Code 44106
===========================================================
We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in the
brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the cervid
prion strain and influenced by the host (human) prion protein (PrP) primary
sequence;
(3) Reliable essays can be established to detect CWD infection in
humans;and
(4) *** CWD transmission to humans has already occurred. *** We will test
these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary
in vitro approaches.
============================================================
Key Molecular Mechanisms of TSEs
Zabel, Mark D.
Colorado State University-Fort Collins, Fort Collins, CO, United States
Abstract Prion diseases, or transmissible spongiform encephalopathies (TSEs),
are fatal neurodegenerative diseases affecting humans, cervids, bovids, and
ovids. The absolute requirement of PrPC expression to generate prion diseases
and the lack of instructional nucleic acid define prions as unique infectious
agents. Prions exhibit species-specific tropism, inferring that unique prion
strains exist that preferentially infct certain host species and confront
transmission barriers to heterologous host species. However, transmission
barriers are not absolute. Scientific consensus agrees that the sheep TSE
scrapie probably breached the transmission barrier to cattle causing bovine
spongiform encephalopathy that subsequently breached the human transmission
barrier and likely caused several hundred deaths by a new-variant form of the
human TSE Creutzfeldt-Jakob disease in the UK and Europe. The impact to human
health, emotion and economies can still be felt in areas like farming, blood and
organ donations and the threat of a latent TSE epidemic. This precedent raises
the real possibility of other TSEs, like chronic wasting disease of cervids,
overcoming similar human transmission barriers. A groundbreaking discovery made
last year revealed that mice infected with heterologous prion strains facing
significant transmission barriers replicated prions far more readily in spleens
than brains6. Furthermore, these splenic prions exhibited weakened transmission
barriers and expanded host ranges compared to neurogenic prions. These data
question conventional wisdom of avoiding neural tissue to avoid prion
xenotransmission, when more promiscuous prions may lurk in extraneural tissues.
Data derived from work previously funded by NIH demonstrate that Complement
receptors CD21/35 bind prions and high density PrPC and differentially impact
prion disease depending on the prion isolate or strain used. Recent advances in
live animal and whole organ imaging have led us to generate preliminary data to
support novel, innovative approaches to assessing prion capture and transport.
We plan to test our unifying hypothesis for this proposal that CD21/35 control
the processes of peripheral prion capture, transport, strain selection and
xenotransmission in the following specific aims.
1. Assess the role of CD21/35 in splenic prion strain selection and host
range expansion.
2. Determine whether CD21/35 and C1q differentially bind distinct prion
strains
3. Monitor the effects of CD21/35 on prion trafficking in real time and
space
4. Assess the role of CD21/35 in incunabular prion trafficking
Public Health Relevance Transmissible spongiform encephalopathies, or prion
diseases, are devastating illnesses that greatly impact public health,
agriculture and wildlife in North America and around the world. The impact to
human health, emotion and economies can still be felt in areas like farming,
blood and organ donations and the threat of a latent TSE epidemic. This
precedent raises the real possibility of other TSEs, like chronic wasting
disease (CWD) of cervids, overcoming similar human transmission barriers. Early
this year Canada reported its first case of BSE in over a decade audits first
case of CWD in farmed elk in three years, underscoring the need for continued
vigilance and research. Identifying mechanisms of transmission and zoonoses
remains an extremely important and intense area of research that will benefit
human and other animal populations.
Funding Agency Agency National Institute of Health (NIH)
Institute National Institute of Allergy and Infectious Diseases (NIAID)
Type High Priority, Short Term Project Award (R56)
Project # 1R56AI122273-01A1
Application # 9211114
Study Section Cellular and Molecular Biology of Neurodegeneration Study
Section (CMND)
Program Officer Beisel, Christopher E
Project Start 2016-02-16
Project End 2017-01-31
Budget Start 2016-02-16
Budget End 2017-01-31
Support Year 1
Fiscal Year 2016
Total Cost
Indirect Cost Institution Name Colorado State University-Fort Collins
Department Microbiology/Immun/Virology
Type Schools of Veterinary Medicine
DUNS # 785979618 City Fort Collins
State CO
Country United States
Zip Code 80523
PMCA Detection of CWD Infection in Cervid and Non-Cervid Species
Hoover, Edward Arthur
Colorado State University-Fort Collins, Fort Collins, CO, United States
Abstract Chronic wasting disease (CWD) of deer and elk is an emerging highly
transmissible prion disease now recognized in 18 States, 2 Canadian provinces,
and Korea. We have shown that Infected deer harbor and shed high levels of
infectious prions in saliva, blood, urine, and feces, and in the tissues
generating those body fluids and excreta, thereby leading to facile transmission
by direct contact and environmental contamination. We have also shown that CWD
can infect some non-cervid species, thus the potential risk CWD represents to
domestic animal species and to humans remains unknown. Whether prions borne in
blood, saliva, nasal fluids, milk, or excreta are generated or modified in the
proximate peripheral tissue sites, may differ in subtle ways from those
generated in brain, or may be adapted for mucosal infection remain open
questions. The increasing parallels in the pathogenesis between prion diseases
and human neurodegenerative conditions, such as Alzheimer's and Parkinson's
diseases, add relevance to CWD as a transmissible protein misfolding disease.
The overall goal of this work is to elucidate the process of CWD prion
transmission from mucosal secretory and excretory tissue sites by addressing
these questions: (a) What are the kinetics and magnitude of CWD prion shedding
post-exposure? (b) Are excreted prions biochemically distinct, or not, from
those in the CNS? (c) Are peripheral epithelial or CNS tissues, or both, the
source of excreted prions? and (d) Are excreted prions adapted for horizontal
transmission via natural/trans-mucosal routes? The specific aims of this
proposal are: (1) To determine the onset and consistency of CWD prion shedding
in deer and cervidized mice; (2); To compare the biochemical and biophysical
properties of excretory vs. CNS prions; (3) To determine the capacity of
peripheral tissues to support replication of CWD prions; (4) To determine the
protease- sensitive infectious fraction of excreted vs. CNS prions; and (5) To
compare the mucosal infectivity of excretory vs. CNS prions. Understanding the
mechanisms that enable efficient prion dissemination and shedding will help
elucidate how horizontally transmissible prions evolve and succeed, and is the
basis of this proposal. Understanding how infectious misfolded proteins (prions)
are generated, trafficked, shed, and transmitted will aid in preventing,
treating, and managing the risks associated with these agents and the diseases
they cause.
Public Health Relevance Chronic wasting disease (CWD) of deer and elk is an
emergent highly transmissible prion disease now recognized throughout the USA as
well as in Canada and Korea. We have shown that infected deer harbor and shed
high levels of infectious prions in saliva, blood, urine, and feces thereby
leading to transmission by direct contact and environmental contamination. In
that our studies have also shown that CWD can infect some non-cervid species,
the potential risk CWD may represents to domestic animal species and humans
remains unknown. The increasing parallels in the development of major human
neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, and
prion diseases add relevance to CWD as a model of a transmissible protein
misfolding disease. Understanding how infectious misfolded proteins (prions) are
generated and transmitted will aid in interrupting, treating, and managing the
risks associated with these agents and the diseases they cause.
Funding Agency Agency National Institute of Health (NIH)
Institute National Institute of Neurological Disorders and Stroke (NINDS)
Type Research Project (R01)
Project # 4R01NS061902-07
Application # 9010980
Study Section Cellular and Molecular Biology of Neurodegeneration Study
Section (CMND)
Program Officer Wong, May Project Start 2009-09-30
Project End 2018-02-28
Budget Start 2016-03-01
Budget End 2017-02-28
Support Year 7
Fiscal Year 2016
Total Cost $409,868
Indirect Cost $134,234 Institution Name Colorado State University-Fort
Collins
Department Microbiology/Immun/Virology
Type Schools of Veterinary Medicine
DUNS # 785979618 City Fort Collins
State CO
Country United States
Zip Code 80523
LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL
THE WRONG PLACES $$$
*** 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).***
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, Valerie 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 long 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 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.
==============
”The occurrence of CWD must be viewed against the contest of the locations
in which it occurred. It was an incidental and unwelcome complication of the
respective wildlife research programmes. Despite it’s subsequent recognition as
a new disease of cervids, therefore justifying direct investigation, no specific
research funding was forthcoming. The USDA veiwed it as a wildlife problem and
consequently not their province!” page 26.
*** PRION 2015 CONFERENCE FT. COLLINS CWD TSE PRION 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.
*** 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.
*** 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.
Scrapie has been known since 1732...tss
2.2 History
Scrapie is not only the prototype of TSEs but also the prion disease with
the longest history of publication. The fi rst authentic report on scrapie was
written in Germany and dates back to year 1750 (Leopoldt 1750 ) . However, a
later publication (Comber 1772 ) even mentions cases in England that occurred
already in 1732. Several authors at later times even referred to much earlier
time periods, spanning from Roman times up to the seventeenth century, but
without giving corresponding references (for a detailed review see Schneider et
al. 2008 ) . Moreover in former times, many sheep diseases were confused with
scrapie. Other dif fi culties were the various names that were used to describe
this disease throughout Europe: “Goggles”, “Ricketts”, “Rubbing Disease” and
“Trotting Disease” in England, “Scratchie” and “Yeukie pine” in Scotland,
“Basqvilla Disease” in Spain, “La maladie convulsive”, “La Tremblante” and
“Prurigo lumbaire” in France, “Rida” in Iceland, “Gnave-og travesjuke” in Norway
and “Gnubberkrankheit”, “Petermännchen”, “Traber” or “Reiberkrankheit” in
Germany. Altogether, at least 42 different names were used in Europe and India
(Schneider et al. 2008 ) for this disease in small ruminants.
The infectious nature of scrapie was already reckoned in the eighteenth
century (Leopoldt 1750 ). In the following decades and centuries, different
transmission routes were discussed in which the sexual intercourse was the most
suspected modus. However, among other causes like atmospheric disturbances, a
few authors proposed a mere coexistence of infected and non-infected animals or
a spontaneous origin of the diseases (Schneider et al. 2008 ) . In addition, a
broad consent existed already in the nineteenth century concerning the role of
hereditary factors for scrapie. Initially, a hereditary predisposition and the
transmission by asymptomatic animals were assumed (Thaer 1821 ; von Richthofen
1821 ) and even the existence of hereditary and non-hereditary scrapie forms was
postulated (von Richthofen 1826 ) .
>>>Close to 200 years ago, James Parkinson published his 1817
monograph entitled “An Essay on the Shaking Palsy”, in which he reported the
first detailed clinical description of the disease that Jean- Martin Charcot
named after him in 1872.<<<
*** An Essay on the Shaking Palsy
Alzheimer’s disease is named after Dr. Alois Alzheimer. In 1906, Dr.
Alzheimer noticed changes in the brain tissue of a woman who had died of an
unusual mental illness. Her symptoms included memory loss, language problems,
and unpredictable behavior. After she died, he examined her brain and found many
abnormal clumps (now called amyloid plaques) and tangled bundles of fibers (now
called neurofibrillary, or tau, tangles).
Creutzfeldt-Jakob disease was first described by Creutzfeldt in 1920 and by
Jakob in 1921. It was set apart as a new entity on the basis of its distinctive
pathological features. Based on 8 cases, Jakob (1923) gave a lucid outline of
the major clinical features.
SWISS MEDICAL WEEKLY
Alzheimer-type brain pathology may be transmitted by grafts of dura mater
26/01/2016 Singeltary comment ;
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
*** Dr. Ness, about this statement ‘The good news is that mad cow seems to
have been eliminated from U.S.-supplied beef’.
please let me inform you, the USDA FDA BSE surveillance, testing, feed ban,
srm removal, was and is extremely flawed.
the USA is awash with TSE prion disease in different species, all of which
are potentially Zoonotic i.e. BSE, atypical BSE, Scrapie, and CWD.
we must not ignore this science anymore.
Transmissible Spongiform Encephalopathy TSE PRION UPDATE
Saturday, July 23, 2016
BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND
SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016
Tuesday, July 26, 2016
Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016
Sunday, July 17, 2016
*** CHRONIC WASTING DISEASE CWD TSE PRION GLOBAL REPORT UPDATE JULY 17 2016
Saturday, May 28, 2016
*** Infection and detection of PrPCWD in soil from CWD infected farm in
Korea Prion 2016 Tokyo ***
Monday, May 02, 2016
*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***
*** NIH awards $11 million to UTHealth researchers to study deadly CWD
prion diseases Claudio Soto, Ph.D. ***
Public Release: 29-Jun-2016
Tuesday, July 12, 2016
Chronic Wasting Disease CWD, Scrapie, Bovine Spongiform Encephalopathy BSE,
TSE, Prion Zoonosis Science History
see history of NIH may destroy human brain collection
I urge everyone to watch this video closely...terry
*** you can see video here and interview with Jeff's Mom, and scientist
telling you to test everything and potential risk factors for humans ***
Sunday, July 24, 2016
Chronic Wasting Disease Prions in Elk Antler Velvet and Marketing of this
Product in Nutritional Supplements for Humans?
Research Project: TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES: THE ROLE OF
GENETICS, STRAIN VARIATION, AND ENVIRONMENTAL CONTAMINATION IN DISEASE CONTROL
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X
Saturday, July 16, 2016
Importation of Sheep, Goats, and Certain Other Ruminants [Docket No.
APHIS-2009-0095]RIN 0579-AD10
WITH great disgust and concern, I report to you that the OIE, USDA, APHIS,
are working to further legalize the trading of Transmissible Spongiform
Encephalopathy TSE Pion disease around the globe.
THIS is absolutely insane. it’s USDA INC.
Monday, June 20, 2016
Specified Risk Materials SRMs BSE TSE Prion Program
Tuesday, July 12, 2016
Chronic Wasting Disease CWD, Scrapie, Bovine Spongiform Encephalopathy BSE,
TSE, Prion Zoonosis Science History
see history of NIH may destroy human brain collection
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
1999 Singeltary to Olympus on concerns about iatrogenic cjd
Wednesday, March 02, 2016
Endoscope Maker Olympus Agrees To $646 Million Settlement Over Kickbacks,
while still ignoring the elephant in the room, CJD TSE PRIONS Health Inc.
Terry S. Singeltary Sr. Bacliff, Texas USA 77518 flounder9@verizon.net
