Evidence for α-synuclein prions causing multiple system atrophy in humans
with parkinsonism
Stanley B. Prusinera,b,c,1, Amanda L. Woermana, Daniel A. Mordesd, Joel C.
Wattsa,b,2, Ryan Rampersauda, David B. Berrya, Smita Patela, Abby Oehlere,
Jennifer K. Lowef, Stephanie N. Kravitzf, Daniel H. Geschwindf,g, David V.
Gliddenh, Glenda M. Hallidayi, Lefkos T. Middletonj, Steve M. Gentlemank, Lea T.
Grinbergb,l, and Kurt Gilesa,b Author Affiliations
aInstitute for Neurodegenerative Diseases, University of California, San
Francisco, CA 94143; bDepartment of Neurology, University of California, San
Francisco, CA 94143; cDepartment of Biochemistry and Biophysics, University of
California, San Francisco, CA 94143; dC. S. Kubik Laboratory for Neuropathology,
Department of Pathology, Massachusetts General Hospital, Boston, MA 02114;
eDepartment of Pathology, University of California, San Francisco, CA 94143;
fCenter for Neurobehavioral Genetics, Center for Autism Research and Treatment,
and Department of Neurology, University of California, Los Angeles, CA 90095;
gDepartment of Human Genetics, University of California, Los Angeles, CA 90095;
hDepartment of Epidemiology and Biostatistics, University of California, San
Francisco, CA 94143; iSchool of Medical Science, Faculty of Medicine, University
of New South Wales, and Neuroscience Research Australia, Randwick, NSW 2031,
Australia; jAgeing Research Unit, School of Public Health, Imperial College
London, London SW7 2AZ, United Kingdom; kCentre for Neuroinflammation and
Neurodegeneration, Department of Medicine, Imperial College London, London SW7
2AZ, United Kingdom; lMemory and Aging Center, University of California, San
Francisco, CA 94143 Contributed by Stanley B. Prusiner, July 22, 2015 (sent for
review May 19, 2015)
Abstract
Authors & Info SI Metrics Related Content PDF PDF + SI
Significance Prions are proteins that assume alternate shapes that become
self-propagating, and while some prions perform normal physiological functions,
others cause disease. Prions were discovered while studying the cause of rare
neurodegenerative diseases of animals and humans called scrapie and
Creutzfeldt–Jakob disease, respectively. We report here the discovery of
α-synuclein prions that cause a more common neurodegenerative disease in humans
called multiple system atrophy (MSA). In contrast to MSA, brain extracts from
Parkinson’s disease (PD) patients were not transmissible to genetically
engineered cells or mice, although much evidence argues that PD is also caused
by α-synuclein, suggesting that this strain (or variant) is different from those
that cause MSA.
snip...
Abstract
Prions are proteins that adopt alternative conformations that become
self-propagating; the PrPSc prion causes the rare human disorder
Creutzfeldt–Jakob disease (CJD). We report here that multiple system atrophy
(MSA) is caused by a different human prion composed of the α-synuclein protein.
MSA is a slowly evolving disorder characterized by progressive loss of autonomic
nervous system function and often signs of parkinsonism; the neuropathological
hallmark of MSA is glial cytoplasmic inclusions consisting of filaments of
α-synuclein. To determine whether human α-synuclein forms prions, we examined 14
human brain homogenates for transmission to cultured human embryonic kidney
(HEK) cells expressing full-length, mutant human α-synuclein fused to yellow
fluorescent protein (α-syn140*A53T–YFP) and TgM83+/− mice expressing α-synuclein
(A53T). The TgM83+/− mice that were hemizygous for the mutant transgene did not
develop spontaneous illness; in contrast, the TgM83+/+ mice that were homozygous
developed neurological dysfunction. Brain extracts from 14 MSA cases all
transmitted neurodegeneration to TgM83+/− mice after incubation periods of ∼120
d, which was accompanied by deposition of α-synuclein within neuronal cell
bodies and axons. All of the MSA extracts also induced aggregation of
α-syn*A53T–YFP in cultured cells, whereas none of six Parkinson’s disease (PD)
extracts or a control sample did so. Our findings argue that MSA is caused by a
unique strain of α-synuclein prions, which is different from the putative prions
causing PD and from those causing spontaneous neurodegeneration in TgM83+/+
mice. Remarkably, α-synuclein is the first new human prion to be identified, to
our knowledge, since the discovery a half century ago that CJD was
transmissible.
neurodegeneration Parkinson's disease synucleinopathies strains
snip...
(37), our transmission data suggest that caution should be exercised when reusing neurosurgical instruments that have been previously used on suspected cases of MSA or PD to minimize any risk for iatrogenic transmission of the disease. Although deep brain stimulation is not commonly used to treat MSA patients, its increasingly wide use to control dyskinesias often found in many patients with advanced PD requires surgical implantation (38) and, as such, may represent a potential risk for human-to-human transmission of α-synuclein prions.
*** 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
THURSDAY, AUGUST 10, 2017
*** Minimise transmission risk of CJD and vCJD in healthcare settings Updated 10 August 2017
http://creutzfeldt-jakob-disease.blogspot.com/2017/08/minimise-transmission-risk-of-cjd-and.html
Alzheimer’s disease, iatrogenic, and Transmissible Spongiform Encephalopathy TSE Prion disease, that is the question ???
>>> The only tenable public line will be that "more research is required’’ <<< >>> possibility on a transmissible prion remains open<<< O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?
[9. Whilst this matter is not at the moment directly concerned with the iatrogenic CJD cases from hgH, there remains a possibility of litigation here, and this presents an added complication. There are also results to be made available shortly (1) concerning a farmer with CJD who had BSE animals, (2) on the possible transmissibility of Alzheimer’s and (3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest.]
http://web.archive.org/web/20040315075058/http://www.bseinquiry.gov.uk:80/files/yb/1992/12/16005001.pdf
snip...see full Singeltary Nature comment here;
http://www.nature.com/nature/journal/v525/n7568/full/nature15369.html#/comments
see Singeltary comments to Plos ;
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
http://www.plosone.org/annotation/listThread.action?root=82860
Ann N Y Acad Sci. 1982;396:131-43.
Alzheimer's disease and transmissible virus dementia (Creutzfeldt-Jakob disease).
Brown P, Salazar AM, Gibbs CJ Jr, Gajdusek DC.
Abstract
Ample justification exists on clinical, pathologic, and biologic grounds for considering a similar pathogenesis for AD and the spongiform virus encephalopathies. However, the crux of the comparison rests squarely on results of attempts to transmit AD to experimental animals, and these results have not as yet validated a common etiology. Investigations of the biologic similarities between AD and the spongiform virus encephalopathies proceed in several laboratories, and our own observation of inoculated animals will be continued in the hope that incubation periods for AD may be even longer than those of CJD.
http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1982.tb26849.x/abstract
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
http://www.tandfonline.com/doi/abs/10.3109/13506129.2015.1095735?journalCode=iamy20
http://betaamyloidcjd.blogspot.com/2015/11/effect-of-heating-on-stability-of.html
Transmission of multiple system atrophy prions to transgenic mice
Joel C. Wattsa,b, Kurt Gilesa,b, Abby Oehlerc, Lefkos Middletond, David T.
Dextere, Steve M. Gentlemane, Stephen J. DeArmonda,c, and Stanley B.
Prusinera,b,1 Author Affiliations
aInstitute for Neurodegenerative Diseases, and Departments of bNeurology
and cPathology, University of California, San Francisco, CA 94143; and dAgeing
Research Unit, School of Public Health and eCentre for Neuroinflammation and
Neurodegeneration, Department of Medicine, Imperial College, London SW7 2AZ,
United Kingdom Contributed by Stanley B. Prusiner, September 30, 2013 (sent for
review August 21, 2013)
Abstract
Free Full Text Authors & Info Figures SI Metrics Related Content In
This Issue PDF PDF + SI
Significance Multiple system atrophy (MSA) is a neurodegenerative disorder
characterized by the accumulation of misfolded α-synuclein protein in glial
cells within the brain. Transgenic mice expressing mutant α-synuclein that were
inoculated with brain homogenate from MSA patients developed clinical,
biochemical, and pathological signs of a neurodegenerative disease, indicating
that MSA is transmissible under certain conditions. This transmissibility is
reminiscent of the human prion disorders, such as Creutzfeldt–Jakob disease, and
suggests that MSA is caused by the accumulation of toxic α-synuclein prions in
the brain.
Next Section Abstract Prions are proteins that adopt alternative
conformations, which become self-propagating. Increasing evidence argues that
prions feature in the synucleinopathies that include Parkinson’s disease, Lewy
body dementia, and multiple system atrophy (MSA). Although TgM83+/+ mice
homozygous for a mutant A53T α-synuclein transgene begin developing CNS
dysfunction spontaneously at ∼10 mo of age, uninoculated TgM83+/− mice
(hemizygous for the transgene) remain healthy. To determine whether MSA brains
contain α-synuclein prions, we inoculated the TgM83+/− mice with brain
homogenates from two pathologically confirmed MSA cases. Inoculated TgM83+/−
mice developed progressive signs of neurologic disease with an incubation period
of ∼100 d, whereas the same mice inoculated with brain homogenates from
spontaneously ill TgM83+/+ mice developed neurologic dysfunction in ∼210 d.
Brains of MSA-inoculated mice exhibited prominent astrocytic gliosis and
microglial activation as well as widespread deposits of phosphorylated
α-synuclein that were proteinase K sensitive, detergent insoluble, and formic
acid extractable. Our results provide compelling evidence that α-synuclein
aggregates formed in the brains of MSA patients are transmissible and, as such,
are prions. The MSA prion represents a unique human pathogen that is lethal upon
transmission to Tg mice and as such, is reminiscent of the prion causing kuru,
which was transmitted to chimpanzees nearly 5 decades ago.
neurodegeneration bioluminescence imaging seeding proteinopathies
snip...
Discussion
In the studies reported here, we demonstrate that a fatal synucleinopathy
can be initiated in Tg(M83+/−:Gfap-luc) mice that do not spontaneously develop a
neurologic illness, by intracerebral inoculation with brain homogenate from MSA
patients. These results parallel recent reports describing the induction of
α-synuclein deposits and dopaminergic neuron loss, but not overt clinical signs
of neurologic dysfunction, in non-Tg mice following inoculation with recombinant
α-synuclein fibrils (25, 26). Our study reveals that self-propagating,
transmissible α-synuclein aggregates (i.e., α-synuclein prions) are formed not
just in Tg mice that overexpress mutant α-synuclein, but also in the brains of
individuals with a degenerative synucleinopathy such as MSA.
Despite the predilection for oligodendrocytic deposition of α-synuclein in
MSA, we did not observe appreciable levels of phosphorylated α-synuclein
deposition in oligodendrocytes within the brains of MSA-inoculated bigenic mice.
This observation suggests that additional human brain-specific factors may be
responsible for encoding the oligodendrocyte-specific tropism of α-synuclein
aggregates in MSA. However, a more simple explanation is that the heterologous
Prnp promoter that drives mutant α-synuclein expression in TgM83 mice does not
engender a native spatial pattern of α-synuclein expression. This difference may
preclude deposition in mature oligodendrocytes, which do not express α-synuclein
mRNA (31). Inoculation of Tg mice expressing A53T mutant human α-synuclein under
the control of the SNCA promoter or even non-Tg mice with MSA brain homogenate
may help to resolve this issue.
Although some investigators prefer to use alternate terms to describe the
recently recognized “prion” proteins involved in PD, Alzheimer’s disease, and
the tauopathies, the shared features of these protein-mediated degenerative
diseases are becoming progressively more apparent. Some terms suggested to
distinguish self-propagating Aβ, tau, and α-synuclein aggregates from those
composed of PrP include “prion-like protein aggregates,” “transmissible
proteins,” “templated proteins,” “prionoids,” “proteopathic seeds,” “misfolded
proteins,” and “protein pathogens” (32, 33). However, we believe that
α-synuclein aggregates fulfill all of the criteria for being labeled a prion.
First, brain homogenates prepared from MSA patients or spontaneously ill
TgM83+/+ mice containing abundant α-synuclein deposits induce the deposition of
insoluble α-synuclein in the brains of recipient Tg(M83+/−:Gfap-luc) mice
following intracerebral inoculation [Figs. 3 and 4 (23, 24)], demonstrating that
α-synuclein aggregates, like PrPSc, are self-propagating. Second, intracerebral
inoculation with samples containing pathological α-synuclein aggregates causes
not only seeding of protein aggregation in the brain, but also the induction of
clinical signs of neurologic dysfunction, indicative of true disease
transmission [Table 1 (23, 24)]. Third, disease can be initiated by recombinant
α-synuclein that had been polymerized into fibrils (24), indicating that
α-synuclein aggregates, like PrP (34), are sufficient to induce disease. Fourth,
transmission of a degenerative synucleinopathy can occur in animals that do not
develop spontaneous illness within their normal lifespan [Figs. 1 and 2 (25,
26)], ruling out disease acceleration as a mechanism of transmission. Together,
these data mount a compelling case for α-synuclein aggregates in the brains of
MSA patients as being prions.
Although α-synuclein aggregates are clearly capable of behaving like prions
at the molecular level, there is currently no evidence to suggest that MSA or
the other human synucleinopathies are transmissible between humans, in contrast
to CJD, which can be transmitted through the use of PrPSc-infected dura mater
grafts or growth hormone preparations (35) as well as the reuse of
PrPSc-contaminated neurosurgical instruments (36). It is currently unknown
whether α-synuclein prions can attach to surgical instruments and to what extent
they may persist following sterilization. Although attempts to transmit PD to
monkeys by intracerebral inoculation were unsuccessful (37), our transmission
data suggest that caution should be exercised when reusing neurosurgical
instruments that have been previously used on suspected cases of MSA or PD to
minimize any risk for iatrogenic transmission of the disease. Although deep
brain stimulation is not commonly used to treat MSA patients, its increasingly
wide use to control dyskinesias often found in many patients with advanced PD
requires surgical implantation (38) and, as such, may represent a potential risk
for human-to-human transmission of α-synuclein prions.
The rapid transmission of the MSA inocula, compared with TgM83+/+ samples,
in Tg(M83+/−:Gfap-luc) mice was surprising for two reasons. First, the MSA
samples do not harbor α-synuclein with the A53T mutation, which is present in
the TgM83 line. For PrPSc prions, even a single amino acid mismatch between
PrPSc in the inoculum and PrPC in the host can dramatically prolong the disease
incubation period (39). Thus, there does not appear to be a substantial
“transmission barrier” between the WT α-synuclein aggregates present in the MSA
inocula and the A53T mutant α-synuclein present in the mice. Second, the levels
of insoluble phosphorylated α-synuclein were much lower in the MSA brains than
in the brains of the spontaneously ill TgM83+/+ mice used as inocula. This
observation could suggest that the most infectious α-synuclein species may
consist of smaller, more soluble assemblies, as has been observed for PrPSc and
Aβ prions (40, 41). However, a more likely explanation for the rapid
transmission of MSA prions is that these α-synuclein aggregates constitute a
distinct “strain” of prion from the aggregates found in spontaneously ill
TgM83+/+ mice. In prion disease, distinct strains are believed to result from
conformational differences in PrPSc (42, 43). Indeed, conformationally distinct
“strains” of recombinant α-synuclein aggregates that possess varying ability to
initiate tau aggregation have recently been identified (44). Thus, the
α-synuclein aggregates found within oligodendrocytes in the brains of MSA
patients may be conformationally distinct from those found in the brains of
TgM83+/+ mice, engendering distinct transmission properties. The rapid
transmissibility of the MSA strain of α-synuclein prions may reflect the fact
that the α-synuclein aggregates are not sequestered in Lewy bodies, which may
constitute a protective mechanism to limit the spread of a distinct group of
strains of α-synuclein prions in PD and DLB.
The successful transmission of MSA prions to Tg(M83+/−:Gfap-luc) mice
described herein represents a unique human neurodegenerative disease that
demonstrates lethality upon transmission to animals and is reminiscent of the
transmission of kuru, CJD, and related diseases to nonhuman primates (45, 46).
Although Aβ and tau prions derived from the brains of Alzheimer’s disease or
tauopathy patients, respectively, stimulate prion formation as detected by
protein aggregation and deposition upon inoculation into susceptible Tg mice,
neither induces overt signs of neurologic disease nor lethality in the recipient
animals (12, 47). Importantly, MSA-inoculated bigenic mice may comprise a
reliable system for assessing the therapeutic efficacy of drugs designed to
target the formation of α-synuclein prions.
Multiple System Atrophy (MSA)
What is Multiple System Atrophy (MSA)?
Multiple system atrophy (MSA) is a rare neurodegenerative disease marked by
a combination of symptoms affecting movement, blood pressure, and other body
functions; hence the label "multiple system" atrophy. According to the American
Autonomic Society, Multiple System Atrophy (MSA) is a sporadic, progressive,
adult-onset disorder characterized by autonomic dysfunction, parkinsonism and
ataxia (a failure of muscular coordination) in any combination.
Symptoms of MSA include:
Orthostatic hypotension,or a significant fall in blood pressure when
standing, causing dizziness, lightheadedness, fainting, or blurred vision
urinary difficulties or constipation motor control symptoms, including tremor,
rigidity, and loss of muscle coordination, loss of balance male impotence
(inability to achieve or maintain an erection) speech or swallowing difficulties
Who gets MSA?
MSA affects both men and women primarily in their 50s.
What causes MSA?
Multiple system atrophy is associated with deterioration and shrinkage
(atrophy) of portions of the brain (cerebellum, basal ganglia and brainstem)
that regulate internal body functions, digestion and motor control.
There is no known cause for brain changes in MSA.
How is MSA diagnosed?
Diagnosis of MSA can be challenging because there is no test that can make
or confirm the diagnosis in a living patient. Certain signs and symptoms of MSA
also occur with other disorders, such as Parkinson's disease, making the
diagnosis more difficult.
If your doctor suspects multiple system atrophy, he or she will obtain a
medical history and perform a physical examination. You may receive a referral
to a neurologist or other specialist for specific evaluations that can help in
making the diagnosis.
Tests that may be helpful in making a diagnosis include:
Tilt table test - In this procedure, your blood pressure is monitored while
you are on a special table that will tilt you to an almost upright position.
This allows the physician to record blood pressure irregularities, and
information about whether they occur with a change in physical position. Blood
tests A sweat test to evaluate perspiration Tests to assess your bladder and
bowel function Electrocardiogram to track the electrical signals of your heart
Brain-imaging tests, particularly a magnetic resonance imaging (MRI) scan, to
determine if another condition might be triggering symptoms Pharmacological
challenge tests (administering certain medications and observing the patient’s
body’s reaction to them, in controlled clinical settings) For patients with
sleep irregularities, particularly if they involve interrupted breathing or
snoring, physicians may recommend an evaluation in a sleep laboratory to
determine if there is an underlying and treatable sleep disorder, such as sleep
apnea.
What is the treatment for MSA?
There is no known cure for MSA, so management of the disease focuses on
treating the more disabling symptoms listed above.
A clinical trial of the drug Rifampicin is being conducted by the Autonomic
Disorders Consortium.
Tuesday, November 26, 2013
Transmission of multiple system atrophy prions
to transgenic mice
Self-Propagative Replication of Ab Oligomers Suggests Potential
Transmissibility in Alzheimer Disease
Received July 24, 2014; Accepted September 16, 2014; Published November 3,
2014
*** Singeltary comment ***
Saturday, March 21, 2015
*** Canada and United States Creutzfeldt Jakob TSE Prion Disease Incidence
Rates Increasing
*** HUMAN MAD COW DISEASE nvCJD TEXAS CASE NOT LINKED TO EUROPEAN TRAVEL
CDC ***
Sunday, November 23, 2014
*** Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas
in June 2014 confirmed as USA case NOT European ***
the patient had resided in Kuwait, Russia and Lebanon. The completed
investigation did not support the patient's having had extended travel to
European countries, including the United Kingdom, or travel to Saudi Arabia. The
specific overseas country where this patient’s infection occurred is less clear
largely because the investigation did not definitely link him to a country where
other known vCJD cases likely had been infected.
Sunday, December 14, 2014
*** ALERT new variant Creutzfeldt Jakob Disease nvCJD or vCJD, sporadic CJD
strains, TSE prion aka Mad Cow Disease United States of America Update December
14, 2014 Report ***
Terry S. Singeltary Sr.
Thursday, July 30, 2015
Professor Lacey believes sporadic CJD itself originates from a cattle
infection number of cattle farmers falling victim to Creutzfeld-Jakob Disease is
much too high to be mere chance
Tuesday, August 4, 2015
FDA U.S. Measures to Protect Against BSE
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS
*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***
O18
Zoonotic Potential of CWD Prions
Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1,
Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve
University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy,
3Encore Health Resources, Houston, Texas, USA
==================
***These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.***
==================
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
================
***This insinuates that, at the level of protein:protein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.***
================
From: Terry S. Singeltary Sr.
Sent: Saturday, November 15, 2014 9:29 PM
To: Terry S. Singeltary Sr.
Subject: THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE R. G. WILL
1984
THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE
R. G. WILL
1984
*** The association between venison eating and risk of CJD shows similar
pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK
OF CJD (p = 0.04). (SEE LINK IN REPORT HERE...TSS) PLUS, THE CDC DID NOT PUT
THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;
snip...
*** These results would seem to suggest that CWD does indeed have zoonotic
potential, at least as judged by the compatibility of CWD prions and their human
PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests
that if zoonotic CWD occurred, it would most likely effect those of the PRNP
codon 129-MM genotype and that the PrPres type would be similar to that found in
the most common subtype of sCJD (MM1).***
*** The potential impact of prion diseases on human health was greatly
magnified by the recognition that interspecies transfer of BSE to humans by beef
ingestion resulted in vCJD. While changes in animal feed constituents and
slaughter practices appear to have curtailed vCJD, there is concern that CWD of
free-ranging deer and elk in the U.S. might also cross the species barrier.
Thus, consuming venison could be a source of human prion disease. Whether BSE
and CWD represent interspecies scrapie transfer or are newly arisen prion
diseases is unknown. Therefore, the possibility of transmission of prion disease
through other food animals cannot be ruled out. There is evidence that vCJD can
be transmitted through blood transfusion. There is likely a pool of unknown size
of asymptomatic individuals infected with vCJD, and there may be asymptomatic
individuals infected with the CWD equivalent. These circumstances represent a
potential threat to blood, blood products, and plasma supplies.
Tuesday, May 26, 2015
*** Minimise transmission risk of CJD and vCJD in healthcare settings
***
Last updated 15 May 2015
Monday, August 17, 2015
FDA Says Endoscope Makers Failed to Report Superbug Problems OLYMPUS
I told Olympus 15 years ago about these risk factors from endoscopy
equipment, disinfection, even spoke with the Doctor at Olympus, this was back in
1999. I tried to tell them that they were exposing patients to dangerous
pathogens such as the CJD TSE prion, because they could not properly clean them.
even presented my concern to a peer review journal GUT, that was going to
publish, but then it was pulled by Professor Michael Farthing et al... see ;
*** now, from all the consumption and exposure above, now think iatrogenic
cjd tse prion at a hospital near you, what if?
Thursday, August 13, 2015
Iatrogenic CJD due to pituitary-derived growth hormone with genetically
determined incubation times of up to 40 years
Saturday, December 13, 2014
*** Terry S. Singeltary Sr. Publications TSE prion disease Peer Review
***
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14,
2001 JAMA
snip...
2017 UPDATE TSE PRION ZOONOSIS
WEDNESDAY, OCTOBER 4, 2017
EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) of the United States of America (USA) a review 2017
http://bseusa.blogspot.com/2017/10/efsa-scientific-report-on-assessment-of.html
MONDAY, OCTOBER 02, 2017
Creutzfeldt Jakob Disease United States of America USA and United Kingdom UK Increasing and Zoonotic Pontential From Different Species
http://creutzfeldt-jakob-disease.blogspot.com/2017/10/creutzfeldt-jakob-disease-united-states.html
THURSDAY, AUGUST 17, 2017
*** Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States revisited 2017
Singeltary et al
http://creutzfeldt-jakob-disease.blogspot.com/2017/08/monitoring-occurrence-of-emerging-forms.html
FRIDAY, AUGUST 11, 2017
Infectivity in bone marrow from sporadic CJD patients
Bioassays in transgenic mice expressing the human prion protein revealed the presence of unexpectedly high levels of infectivity in the bone marrow from seven out of eight sCJD cases. These findings may explain the presence of blood-borne infectivity in sCJD patients. They also suggest that the distribution of prion infectivity in peripheral tissues in sCJD patients could be wider than currently believed, with potential implications for the iatrogenic transmission risk of this disease.
http://creutzfeldt-jakob-disease.blogspot.com/2017/08/infectivity-in-bone-marrow-from.html
THURSDAY, AUGUST 10, 2017
*** Minimise transmission risk of CJD and vCJD in healthcare settings Updated 10 August 2017
http://creutzfeldt-jakob-disease.blogspot.com/2017/08/minimise-transmission-risk-of-cjd-and.html
National Prion Center could lose all funding just as concern about CWD jumping to humans rises
SATURDAY, JULY 15, 2017
*** National Prion Center could lose all funding just as concern about CWD jumping to humans rises
http://creutzfeldt-jakob-disease.blogspot.com/2017/07/national-prion-center-could-lose-all.html
Terry S. Singeltary Sr.
Terry S. Singeltary Sr.
