transmission or seed ???
iatrogenic ???
what if ???
Prion 7:1, 55–59; January/February 2013; © 2013 Landes Bioscience MINI-rev
iew Mini-REVIEW
Prions, prionoids and pathogenic proteins in Alzheimer disease
Karen H. Ashe1,2,3,* and Adriano Aguzzi4
1Department of Neurology; N. Bud Grossman Center for Memory Research and
Care; University of Minnesota; Minneapolis, MN USA; 2Department of Neuroscience;
N. Bud Grossman Center for Memory Research and Care; University of Minnesota;
Minneapolis, MN USA; 3GRECC; VA Medical Center; Minneapolis, MN USA; 4Institute
of Neuropathology; University Hospital Zurich; Zurich, Switzerland Keywords:
prions, prionoids, PrP, amyloid-β, tau, pathogenic proteins, Alzheimer disease
Like patients with prion disease, Alzheimer patients suffer from a fatal,
progressive form of dementia. There is growing evidence that amyloid-β (Aβ)
aggregates may be transmissible similar to prions, at least under extreme
experimental conditions. However, unlike mice infected with prion protein (PrP)
prions, those inoculated with Aβ do not die. The transmission of Aβ and PrP thus
differs conspicuously in the neurological effects they induce in their hosts,
the difference being no less than a matter of life and death. Far from being a
mere academic nuance, this distinction between Aβ and PrP begs the crucial
questions of what, exactly, controls prion toxicity and how prion toxicity
relates to prion infectivity.
Prions in Neurological Disease
Stanley Prusiner introduced prions in 1982 as the self-replicating forms of
the prion protein that accumulate in certain transmissible diseases of the
central nervous system, such as scrapie and Creutzfeldt-Jakob disease.1 Although
prions represent novel infectious agents lacking pathogen-encoded nucleic acids,
their discovery relied upon a century-old paradigm, formalized into postulates
by Robert Koch, for identifying pathological microbial agents. A key concept in
Koch’s postulates is that the microbe responsible for a given disease must cause
that same disease when inoculated into a susceptible host. In prion disease, the
afflicted individual suffers from a progressive deterioration in neurological
function that culminates, inevitably, in death. By systematically sifting
through brain extracts from scrapie-infected hamsters, Prusiner found that the
deadliest inoculates contained fibrillar aggregates of a proteolytic fragment of
the prion protein, PrP27- 30. We now know that this fragment is derived from the
scrapie isoform of the prion protein, PrPSc, an aggregated, alternatively folded
conformer of the cellular prion protein, PrPC.2
In 2000, Lary Walker first demonstrated that intra-cerebral inoculations of
brain extracts from amyloid plaque-containing brain tissue from Alzheimer
patients accelerate amyloid plaque deposition and β-amyloidosis in transgenic
mice expressing human Aβ proteins.3 The acceleration of β-amyloidosis by
inoculates containing Aβ fibrils, which form amyloid plaques, has been
replicated in at least four other laboratories using inoculates from humans,
several lines of plaque-forming transgenic mice and, most recently, fibrillar
synthetic Aβ aggregates and synthetic Aβ dimers.4-7
While these results indicate that fibrillar conformers of Aβ proteins can
self-replicate in susceptible hosts, it is still unclear whether such
replication can be maintained over multiple serial passages from one animal to
another. The latter is an integral part of the definition of a “prion.” For the
sake of the following discussion, we will refer to PrPSc as the aggregated form
of PrPC found in transmissible spongiform encephalopathies (TSEs), and to
“prions” as the infectious agent of TSEs as measured with microbiological
methods. In this frame of reference, prions are composed of PrPSc, but not all
PrPSc is necessarily infectious.8
Infectious Agents, Prions and Prionoids
In 1966 Carlton Gajdusek astonished the scientific world with the claim
that the fatal degenerative disease kuru was transmitted through ritualistic
cannibalism among the Fore peoples of New Guinea;9 the proposal that the elusive
infectious agent in kuru was a prion was no less surprising. Now, however, the
radical properties ascribed to prions threaten to undermine the original meaning
of “infectious agent.” In the following discussion, an infectious agent
transmits a disease causing deficits in the host that are the same as those in
the donor and share the same pathophysiology. Simply put, infectious agents are
the biological basis of ill health that can be passed between living beings.
Prions fulfill the above definition since they were initially discovered as
true infectious agents using microbiological methods. However, many other
proteins can aggregate into geometrically arranged structures that can seed—in
vitro and in vivo—compartments containing the parent protein in a monomeric
soluble state.
Simply equating the capability of seeding with the term “prion” is an
oversimplification. Any inorganic crystal can seed a supersaturated solution of
its cognate salt, whereas bona fide prions have caused epidemics in sheep, cows,
mink, felines and humans (kuru, as well as iatrogenic and “variant” Creutzfeldt-
Jakob disease). Because of their flagrant infectious traits—communicability and
contagiousness—the agents of these diseases were not recognized as prions for
many decades, and many preeminent scientists deemed them to be “slow viruses.”
Since none of the newly discovered seeded aggregates have yet been shown to
be infectious (i.e., communicable or contagious) under natural conditions, we
deem it prudent to refer to them as “prionoids.”10,11 Maintaining a distinction
between prions and prionoids implies the existence of underlying biological
processes that govern the natural transmission of diseases between organisms,
including the sophisticated mechanisms by which extraneural inoculations of
prions subvert the immune system to reach and damage the brain (reviewed by
Aguzzi and Calella12).
Fortunately, there is no indication that such processes exist for Aβ
prionoids. However, the demonstration of inter-individual transmissibility would
warrant upgrading the status of such agents to bona fide prions, as seems very
likely to occur in the case of AA amyloid.13
SNIP...
With the exception of PrPSc, there is no experimental evidence that the
prions or prionoids in neurodegenerative diseases are the pathogenic proteins
[star (*) proteins] inducing the neurological deterioration that devastates
patients. For a hundred years, neurofibrillary tangles—the intracellular amyloid
inclusions that form when tau takes on novel β-sheet structure—were believed to
induce neuron death and impair cognition. However, in 2005 this hundred-year-old
hypothesis was disproven when it was shown that reducing soluble tau in a
neurodegenerative mouse model with neurofibrillary tangles led to the cessation
of neuron loss and the improvement of memory function, in spite of the startling
observation that the neurofibrillary tangles kept accumulating, reminiscent of
prionoids.14 The negative case for β-amyloid plaques containing *proteins stems
from multiple lines of evidence, including the failure of Alzheimer patients to
improve following Aβ immunotherapy that nonetheless successfully removed amyloid
plaques,15 and the ability of immunotherapy to reverse deficits in mice without
changing plaque load.16,17 Compared with the proteins comprising amyloid
lesions, prions, and prionoids, relatively little is known about *proteins and
their mechanisms of action.
SNIP...
The conclusion that the removal of the inclusions would not cure familial
ataxia type 1 prompted Harry Orr and Huda Zoghbi to search for the pathogenic
form of PolyQ/ataxin-1 causing the neurological abnormalities in the disorder.
Discovering the mechanism by which PolyQ/ataxin-1 damages neurons emerged from
understanding the normal physiological roles of ataxin-1, which is a nuclear
protein. The pathogenic form of PolyQ/ataxin-1 is not a misfolded form of
ataxin-1; it contains no novel secondary structures, no β-sheets that are not
normally present in the brain. Its pathological effects arise from alterations
in its binding affinities with its normal nuclear partners, the transcriptional
regulator Capicua and the regulator of RNA splicing RMB17,22 leading to changes
in the transcriptome that, presumably, affect neuronal function and viability.
Thus, the pathogenic form of PolyQ/ataxin-1 is not a prionoid; it is neither a
misfolded protein nor a soluble aggregate of the parent protein.
_This may prove to be a profoundly important lesson for the entire field of
neurodegenerative disease research._
SNIP...
A Puzzle and Two Hypotheses Both patients with prion disease and Alzheimer
disease suffer from fatal, progressive forms of dementia. However, while mice
infected with PrP prions die, those inoculated with Aβ prions do not. Only two
hypotheses can explain the stark contrast between the fatality rates caused by
PrP and Aβ inoculations in mice. • Hypothesis 1: all aggregated proteins (prions
and prionoids) are bad. Aggregates are pathogenic, but different aggregates
exert their effects on different cellular pathways. For example, the pathogenic
pathway for Aβ aggregates in humans, distinct from that of PrP prions, may not
exist in mice. • Hypothesis 2: not all aggregates are bad. Aggregates are not
invariably pathogenic; rather, variants of parent proteins (*proteins) cause the
cellular dysfunction that leads to a neurological illness (Fig. 1). These
pathogenic variants need not be misfolded or aggregated forms of the parent
proteins. Recent advances in our understanding of the neurotoxicity of PrP and
Aβ favor hypothesis 2, as discussed below.
SNIP...
Figure 1. Prions, prionoids and pathogenic proteins in neurodegenerative
diseases. PrPSc is considered to be the transmissible agent of the prion causing
scrapie, Creutzfeldt-Jakob disease and related spongiform encephalopathies.
Nucleating fibrillar protein aggregates (“prionoids”) are found in many
neurodegenerative diseases. With the exception of PrPSc, there is little
evidence in mice or humans linking prionoids in the brain to the
pathophysiological processes that cause the disorders connected with these
proteins. Instead, accumulating data indicate that the brain dysfunction and
neurological signs associated with these illnesses are caused by non-fibrillar
variants of the parent proteins (*proteins). In the case of Aβ, brain
dysfunction in mice and CSF tau abnormalities in humans are strongly associated
with a soluble 56-kDa assembly, Aβ*. The existence of other Aβ* molecules has
not been excluded. The *proteins need not be misfolded in the sense of adopting
novel secondary structure, which invariably involves β-sheets. PolyQ/ataxin-1 is
the best example. Distinguishing between prionoids and *proteins, and
understanding how *proteins cause neurological illness, will advance our
progress in treating these profoundly devastating and fatal disorders.
SNIP...
There has been recurrent discussion as to whether the self-replicating
material in prion disease (the “prion”) is physically identical with the
neurotoxic entity. In this context, John Collinge has recently proposed the term
“PrPL” to denote a hypothetical moiety that may be neurotoxic yet differs from
PrPSc.24 However, the idea that PrP may produce neurological disease without the
generation of infectivity dates back to 1990 when transgenic mice that
spontaneously developed prion disease were created. These mice expressed PrP
carrying a mutation linked to a familial prion disease, developed ataxia,
lethargy and rigidity, and invariably died, but their brains contained few or no
infectious prions, suggesting that “an inborn error of PrP metabolism could
produce neurologic disease without the generation of infectivity.” 25 It is
possible, and indeed very likely in our view, that PrPSc and the various
non-infectious neurotoxic variants of PrP, which include PrP with supernumerary
octapeptide repeats26 and PrP versions with interstitial deletions of the
“hinge” region between the unstructured N-terminus and the globular domain,27
activate neurotoxic pathways converging with those triggered by prion infection
(Fig. 2).
SNIP...
In the absence of animal models, harboring Alzheimer-related mutations
exclusively, that exhibit the full spectrum of disease, beginning with subtle
neuronal dysfunction and culminating with fatal cognitive devastation, the
question of whether asymptomatic β-amyloidosis requires Aβ*56 to develop into
full-blown Alzheimer disease cannot be addressed experimentally. It is possible
that one or more non-prionoid form of Aβ triggers neuronal dysfunction and
neurodegeneration in Alzheimer disease. Discovering these pathogenic forms will
depend upon the creation of high fidelity model systems of Alzheimer disease.
Conclusion
In bona fide prion diseases, a very large body of evidence links the
aggregated form of PrP, PrPSc, to both prion infectivity and prion
neurotoxicity. However, non-infectious, yet neurotoxic, variants of PrP occur
naturally and more such variants have been constructed experimentally,
indicating that the phenotypic expression typical of prion diseases can be
triggered by events occurring downstream of prion infection. There is little
evidence in mice or humans linking the neurological effects of Aβ to the
nucleating forms of this protein, while emerging data point to a specific
non-nucleating form of Aβ, Aβ*56, that produces some of the neurological signs
of disease. However, Aβ*56 is not sufficient to induce the inexorable
neurological deterioration that characterizes Alzheimer disease, indicating that
other critical factors or forms of Aβ work in collaboration with Aβ*56 to
destroy the brain. Curing prion and Alzheimer disease will depend upon
developing a deeper understanding of the pathogenic forms of PrP and Aβ that
cause the brain dysfunction underlying these deadly illnesses.
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.
CJD1/9 0185 Ref: 1M51A
IN STRICT CONFIDENCE
Dr McGovern From: Dr A Wight Date: 5 January 1993 Copies: Dr Metters Dr
Skinner Dr Pickles Dr Morris Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4
January, to discuss the above findings. It was chaired by Professor Murray
(Chairman of the MRC Co-ordinating Committee on Research in the Spongiform
Encephalopathies in Man), and attended by relevant experts in the fields of
Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the
spongiform encephalopathies, and by representatives of the MRC and AFRC. 2.
Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of p amyloid in
primates were valid, interesting and a significant advance in the understanding
of neurodegenerative disorders;
ii) there were no immediate implications for the public health, and no
further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the
molecular level. Possible avenues are being followed up by DH and the MRC, but
the details will require further discussion. 93/01.05/4.1
BSE101/1 0136
IN CONFIDENCE
5 NOV 1992 CMO From: Dr J S Metters 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
recognized 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 emphasizes 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.
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.
JS METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832
121/YdeS 92/11.4/1.2
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight Date: 5 January 1993
Copies:
Dr Metters Dr Skinner Dr Pickles Dr Morris Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
Tuesday, October 4, 2011
Molecular Psychiatry
advance online publication 4 October 2011; doi: 10.1038/mp.2011.120
De novo induction of amyloid-ß deposition in vivo
Our results suggest that some of the typical brain abnormalities associated
with AD can be induced by a prion-like mechanism of disease transmission through
propagation of protein misfolding. These findings may have broad implications
for understanding the molecular mechanisms responsible for the initiation of AD,
and may contribute to the development of new strategies for disease prevention
and intervention.
Keywords: amyloid; prion; protein misfolding; disease transmission
Wednesday, January 5, 2011
ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions
David W. Colby1,* and Stanley B. Prusiner1,2
ONLINE FIRST
Evaluation of Potential Infectivity of Alzheimer and Parkinson Disease
Proteins in Recipients of Cadaver-Derived Human Growth Hormone
David J. Irwin, MD; Joseph Y. Abrams, MPH; Lawrence B. Schonberger, MD,
MPH; Ellen Werber Leschek, MD; James L. Mills, MD, MS; Virginia M.-Y. Lee, PhD,
MBA; John Q. Trojanowski, MD, PhD JAMA Neurol. 2013;():1-7.
doi:10.1001/jamaneurol.2013.1933.
Published online February 4, 2013
Importance Growing evidence of cell-to-cell transmission of
neurodegenerative disease (ND)–associated proteins (NDAPs) (ie, tau, Aβ, and
α-synuclein) suggests possible similarities to the infectious prion protein
(PrPsc) in spongiform encephalopathies. There are limited data on the potential
human-to-human transmission of NDAPs associated with Alzheimer disease (AD) and
other non-PrPsc ND.
Objective To examine evidence for human-to-human transmission of AD,
Parkinson disease (PD), and related NDAPs in cadaveric human growth hormone
(c-hGH) recipients.
Design We conducted a detailed immunohistochemical analysis of pathological
NDAPs other than PrPsc in human pituitary glands. We also searched for ND in
recipients of pituitary-derived c-hGH by reviewing the National Hormone and
Pituitary Program (NHPP) cohort database and medical literature.
Setting University-based academic center and agencies of the US Department
of Health and Human Services.
Participants Thirty-four routine autopsy subjects (10 non-ND controls and
24 patients with ND) and a US cohort of c-hGH recipients in the NHPP.
Main Outcome Measures Detectable NDAPs in human pituitary sections and
death certificate reports of non-PrPsc ND in the NHPP database.
Results We found mild amounts of pathological tau, Aβ, and α-synuclein
deposits in the adeno/neurohypophysis of patients with ND and control patients.
No cases of AD or PD were identified, and 3 deaths attributed to amyotrophic
lateral sclerosis (ALS) were found among US NHPP c-hGH recipients, including 2
of the 796 decedents in the originally confirmed NHPP c-hGH cohort database.
Conclusions and Relevance Despite the likely frequent exposure of c-hGH
recipients to NDAPs, and their markedly elevated risk of PrPsc-related disease,
this population of NHPP c-hGH recipients does not appear to be at increased risk
of AD or PD. We discovered 3 ALS cases of unclear significance among US c-hGH
recipients despite the absence of pathological deposits of ALS-associated
proteins (TDP-43, FUS, and ubiquilin) in human pituitary glands. In this unique
in vivo model of human-to-human transmission, we found no evidence to support
concerns that NDAPs underlying AD and PD transmit disease in humans despite
evidence of their cell-to-cell transmission in model systems of these disorders.
Further monitoring is required to confirm these conclusions.
"By interrogating an existing database with information on a cohort of
well-characterized patients, we were able to determine that there is no evidence
suggesting the pathology of Alzheimer's or Parkinson's can transmit between
humans," said senior author John Q. Trojanowski, MD, PhD, professor of Pathology
and Laboratory Medicine and co-director of the Penn Center for Neurodegenerative
Disease Research." ...
really ???
From: Terry S. Singeltary Sr.
Sent: Tuesday, February 05, 2013 10:56 AM
To: evpdean@mail.med.upenn.edu ; ljameson@mail.med.upenn.edu
Cc: kim.menard@uphs.upenn.edu ; Karen.kreeger@uphs.upenn.edu ;
VMYLEE@MAIL.MED.UPENN.EDU ; evpdean@mail.med.upenn.edu ;
mattera@mail.med.upenn.edu ; trojanow@mail.med.upenn.edu ;
karen.kreeger@uphs.upenn.edu ; jessica.mikulski@uphs.upenn.edu ;
holly.auer@uphs.upenn.edu ; katie.delach@uphs.upenn.edu ;
katie.delach@uphs.upenn.edu ; katie.delach@uphs.upenn.edu ;
katie.delach@uphs.upenn.edu
Subject: Penn study confirms no transmission of Alzheimer's proteins
between humans ?
Penn study confirms no transmission of Alzheimer's proteins between humans
?
Contact: Kim Menard kim.menard@uphs.upenn.edu 215-662-6183 University of
Pennsylvania School of Medicine
Penn study confirms no transmission of Alzheimer's proteins between humans
PHILADELPHIA - Mounting evidence demonstrates that the pathological
proteins linked to the onset and progression of neurodegenerative disorders are
capable of spreading from cell-to-cell within the brains of affected individuals
and thereby "spread" disease from one interconnected brain region to another. A
new study found no evidence to support concerns that these abnormal disease
proteins are "infectious" or transmitted from animals to humans or from one
person to another. The study by researchers from the Perelman School of Medicine
at the University of Pennsylvania, in conjunction with experts from the U.S.
Centers for Disease Control and the Department of Health and Human Services,
appears online in JAMA Neurology.
Cell-to-cell transmission is a potentially common pathway for disease
spreading and progression in diseases like Alzheimer's (AD) and Parkinson's (PD)
disease as well as frontotemporal lobar degeneration (FTLD), amyotrophic lateral
sclerosis (ALS) and other related disorders. It appears that misfolded proteins
spread from one cell to another and that the affected neurons become
dysfunctional, while these toxic proteins go on to damage other regions of the
brain over time.
"By interrogating an existing database with information on a cohort of
well-characterized patients, we were able to determine that there is no evidence
suggesting the pathology of Alzheimer's or Parkinson's can transmit between
humans," said senior author John Q. Trojanowski, MD, PhD, professor of Pathology
and Laboratory Medicine and co-director of the Penn Center for Neurodegenerative
Disease Research. "We can now redouble efforts to find treatments, via
immunotherapies or other approaches to stop the spreading of these toxic
proteins between cells."
In order to verify whether such proteins could potentially be carried from
person to person, the team of researchers analyzed data from an existing cohort
of patients who had received human growth hormone (hGH) from cadaveric pituitary
glands via a national program, as a beneficial treatment for stunted growth,
before synthetic hGH was available. Nearly 7,700 patients were treated with
cadaver-derived hGH (c-hGH) in the US between 1963 and 1985. In the mid-1980s,
more than 200 patients worldwide who had received c-hGH inadvertently
contaminated with prion proteins from affected donor pituitary tissue went on to
develop an acquired form of Creutzfeldt-Jakob disease (CJD), a rare,
degenerative, invariably fatal brain disorder caused by pathological prion
proteins that also are the cause of Mad Cow disease. Since then, the cohort has
been followed to track any additional cases of CJD, with extensive medical
histories for patients over the 30+ years since the c-hGH therapy was stopped
after the link to CJD was discovered in 1985.
In this current study, researchers looked for signs of an elevated risk of
AD, PD, FTLD or ALS among this group and found that none of the c-hGH recipients
developed AD, PD or FTLD. The team did identify three ALS cases of unclear
significance, given that no traces of ALS disease proteins (TDP-43, FUS and
Ubiquilin) were found in human pituitary glands, despite the presence of
pathological AD (tau, Aβ) and PD (alpha-synuclein) proteins. This clarified that
c-hGH recipients were most likely exposed to these neurodegenerative disease
proteins linked to AD, PD and FTLD but this did not result in transmission of
disease from person to person.
"This cohort is an invaluable resource and should continue to be followed,
especially as we rapidly increase our understanding of disease progression in
neurodegenerative conditions," said David Irwin, MD, lead author, and fellow in
the Center for Neurodegenerative Disease Research and the department of
Neurology in the Perelman School of Medicine.
###
The other co-authors of this study are Joseph Y. Abrams, Lawrence B.
Schonberger, Ellen W. Leschek, James L. Mills, and Virginia M.-Y. Lee. This
research was supported by grants from the National Institute on Aging (P30
AG010124, Alzheimer's Core Center grant, T32-AG000255), Intramural Research
Program and National Institute of Child Health and Development at the National
Institutes of Health.
Penn Medicine is one of the world's leading academic medical centers,
dedicated to the related missions of medical education, biomedical research, and
excellence in patient care. Penn Medicine consists of the Raymond and Ruth
Perelman School of Medicine at the University of Pennsylvania (founded in 1765
as the nation's first medical school) and the University of Pennsylvania Health
System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine is currently ranked #2 in U.S. News &
World Report's survey of research-oriented medical schools. The School is
consistently among the nation's top recipients of funding from the National
Institutes of Health, with $479.3 million awarded in the 2011 fiscal year.
The University of Pennsylvania Health System's patient care facilities
include: The Hospital of the University of Pennsylvania -- recognized as one of
the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn
Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first
hospital, founded in 1751. Penn Medicine also includes additional patient care
facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety
of community-based programs and activities. In fiscal year 2011, Penn Medicine
provided $854 million to benefit our community.
Penn study confirms no transmission of Alzheimer's proteins between humans
?
confused ???
Greetings Jama, Penn state, Perelman School of Medicine Deans et al,
eurekalert, Authors et al,
In my opinion, this subject title (NOT a transmission study, but only a
study a team of researchers did by analyzed data from hGH recipients years,
decades ago), and it’s interpretations, as described by Kim Menard
“Penn study confirms no transmission of Alzheimer's proteins between
humans” ,
IN my opinion, is false.
In my opinion, this study does not prove or confirm that Alzheimer’s does
not transmit to humans. your title is very misleading in my opinion. very
confusing, as the title here stipulated from eurekalert. Penn state DID NOT
confirm or prove that Alzheimer’s proteins are NOT transmissible between humans,
of the contrary, there is indeed science showing that Alzheimer’s disease IS
transmissible. I am very close to all this, please see ;
Penn Study: Transmission of Tangles in Alzheimer's Mice Provides More
Authentic Model of Tau Pathology
January 16, 2013
snip...
The study demonstrates that synthetic tau fibrils alone are capable of
inducing authentic NFT-like tau clumps and initiating spreading of tau pathology
in an Alzheimer’s mouse model.
Transmission of Tangles in Alzheimer's Mice Provides More Authentic Model
of Tau Pathology, Penn Study Shows
New Model Provides First Step in Generating New Therapies
Friday, February 15, 2013
Scottish TSE Network November Symposium Announcement Event: 12 November
2012 Title: Is Alzheimer’s Disease a transmissible disease? SUMMARY
Cell to cell spread of misfolded protein
A meeting was held on the 12th November hosted by the Scottish
Transmissible Spongiform Encephalopathy Network (STN) at the Roslin Institute,
University of Edinburgh with the aim of examining whether Alzheimer's disease
should be classed as a “transmissible disease”? Speakers included international
experts in prion and Alzheimer's diseases examining the evidence from studies in
the human population and in animal models. The presentations reviewed the
current position and the final discussion drew some important conclusions.
It is well known that in prion diseases an abnormal misfolded protein
(PrPSc) derived from a normal host protein (PrPC) accumulates and spreads
through the brain along defined neuroanatomical pathways. Prion diseases affect
both animals (scrapie in sheep, BSE in cattle, chronic wasting disease in deer)
and humans (Creutzfeldt - Jakob Disease (CJD)). Transmission between individuals
in the natural state has been observed for some prion diseases, for example in
sheep and deer. Many, although not all, prion diseases in animals can be
experimentally transmitted from animal to animal, and one has transmitted from
animal to human,BSE. CJD can also be transmitted to experimental animals.
However, transmission of CJD between humans only occurs very rarely and in
exceptional circumstances such as the transfer of tissue from an individual with
CJD to another by a surgical procedure or via certain medical treatments.
Transmission between individuals and spread from cell to cell within an
individual, have both been termed “prion transmission”.
It has been shown in neuropathological studies of brains from patients with
Alzheimer’s disease that the pathology also spreads in a predictable way through
the brain. This spread of pathology in the grey matter of the brain involves the
formation of amyloid plaques, comprised of A, outside nerve cells, and
neurofibrillary tangles inside nerve cells. Mice carrying human genes that lead
to the deposition of the A peptide in the brain have been used to study aspects
of Alzheimer’s disease pathology. Experimental studies show that injection of A
plaque material, isolated from a human Alzheimer’s disease brain, or another
mouse with A plaques can accelerate the deposition of A in the brain and its
deposition along neuronal pathways. This predictable spread from cell to cell
has been referred to as “prion-like transmission” and has now been demonstrated
not only in mouse models with the A protein, but also in other models of
neurodegenerative disease that involve the misfolding of proteins. It was
suggested by several of the speakers that the injected misfolded peptide or
protein acts as a “seed” for further deposition of misfolded protein akin to the
growth of a crystal. It is likely that there are considerable parallels between
prion diseases and Alzheimer’s disease in the molecular and cellular events
leading to cell to cell transmission.
There is no evidence to date from analysis of patient populations that
transmission of Alzheimer’s disease between individuals has occurred. It was
concluded that human to human transmission of any protein misfolding disease
requires a set of very unusual circumstances to occur, as has been documented in
the prion diseases. The evidence from human and animal studies does not support
the idea that Alzheimer's disease is transmissible between individuals. The term
“prion-like transmission” has been unhelpful in the context of Alzheimer’s
disease and other protein misfolding diseases as it does not distinguish between
spread between cells and transmission between individuals. The meeting concluded
that the term “prion-like cell to cell spread” should be used to convey a clear
message. The robust experimental models in prion disease provide an opportunity
to understand the cellular and molecular mechanisms of cell to cell spread and
identify therapeutic targets to delay disease progression for both prion and
Alzheimer’s disease.
Professor Jean Manson, The Roslin Institute, University of Edinburgh and
R(D)SVS Easter Bush Professor Hugh Perry, University of Southampton
END...TSS
UPDATE JUNE 28, 2012
Scottish TSE Network November Symposium Announcement Event: 12 November
2012
Chair: Prof Hugh Perry, University of Southampton, Southampton UK
Location: The Roslin Institute Building Auditorium
If you would like to book a place at this event, please let Gila Holliman
know.
Cost: £125.
Title: Is Alzheimer’s Disease a transmissible disease?
Speakers:
Session 1:
Prof Bob Will, National CJD Surveillance Unit, Edinburgh UK
Prof James Ironside, National CJD Surveillance Unit, Edinburgh UK
Prof Lary Walker, Emory School of Medicine, Atlanta USA
Session 2:
Prof Mathias Jucker, Hertie Institute for Clinical Brain Research,
Stuttgart Germany
Prof William Van Nostrand, Stony Brook University, Stony Brook USA
Dr Claudio Soto, University of Texas Medical School, Houston USA
Session 3:
Dr Fabrizio Tagliavini, Instituto Neurologico Carlo Besta, Milan Italy
Prof Pedro Piccardo, Food and Drug Administration, Washington DC USA
Dr Bruce Chesebro, National Institutes of Health, Missoula USA
Friday, February 15, 2013
Scottish TSE Network November Symposium Announcement Event: 12 November
2012 Title: Is Alzheimer’s Disease a transmissible disease? SUMMARY
Sunday, February 10, 2013
Parkinson's Disease and Alpha Synuclein: Is Parkinson's Disease a
Prion-Like Disorder?
Sunday, December 9, 2012
Prions, prionoids and pathogenic proteins in Alzheimer disease
Transmission of Prions and Alzheimer’s disease Abeta Amyloid
Claudio Soto, PhD
Mitchell Center for Alzheimer’s disease and Related Brain Disorders, Dept
of Neurology
University of Texas Medical School at Houston
Tuesday, October 4, 2011
Molecular Psychiatry
advance online publication 4 October 2011; doi: 10.1038/mp.2011.120
De novo induction of amyloid-ß deposition in vivo
Our results suggest that some of the typical brain abnormalities associated
with AD can be induced by a prion-like mechanism of disease transmission through
propagation of protein misfolding. These findings may have broad implications
for understanding the molecular mechanisms responsible for the initiation of AD,
and may contribute to the development of new strategies for disease prevention
and intervention. Keywords: amyloid; prion; protein misfolding; disease
transmission
see more here ;
Wednesday, March 28, 2012
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion
poker goes up again $
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
Monday, September 26, 2011
Variably Protease-Sensitive Prionopathy, Prionpathy, Prionopathy, FFI, GSS,
gCJD, hvCJD, sCJD, TSE, PRION, update 2011
===============================
please note, the term prionpathy was first used, then changed to
prionopathy for this type prion disease.
this is not the first time the prion names have changed i.e. nvCJD changed
to vCJD. ...tss
PSPr: Protease-sensitive prionpathy (Gambetti et al, Ann Neurol 2008;
63:697-708)
American Association of Neuropathologists, Inc.: Abstracts o ...
journals.lww.com › Home › May 2009 - Volume 68 - Issue 5
American Association of Neuropathologists, Inc.: Abstracts of the 85th
Annual Meeting June 11-14, 2009 San Antonio, Texas
As sporadic Creutzfeldt-Jakob disease (CJD), this novel prion disease,
named "Protease-Sensitive Prionpathy (PSPr)", includes at least three subtypes
... end
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and
VPSPr PRIONPATHY
Thursday, August 12, 2010
Seven main threats for the future linked to prions
Original Article
A novel human disease with abnormal prion protein sensitive to
protease
Article first published online: 20 JUN 2008
DOI: 10.1002/ana.21420
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
Wednesday, May 16, 2012
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Proposal ID: 29403
Friday, September 3, 2010
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids,
Prionpathy, Prionopathy, TSE
Wednesday, September 21, 2011
PrioNet Canada researchers in Vancouver confirm prion-like properties in
Amyotrophic Lateral Sclerosis (ALS)
SCENARIO 3: ‘THE THIN STEMMED GLASS’
... a TSE is found that is linked to Alzheimer’s disease.
Saturday, February 16, 2013
What’s to like about the prion-like hypothesis for the spreading of
aggregated α-synuclein in Parkinson disease?
Thursday, January 17, 2013
TSE guidance, surgical, dental, blood risk factors, Part 4 Infection
control of CJD, vCJD and other human prion diseases in healthcare and community
settings (updated January 2013)
The Center For Consumer Freedom
Posted On December 20, 2003
--------------------------------------------------------------------------------
Mad Cow Scaremongers
snip...
Like many activists, Singletary ignores overwhelming epidemiological and
laboratory evidence that rules out a connection between sporadic CJD and beef.
Relying entirely on shallow circumstantial evidence and frequent repetition of
claims which have been publicly refuted as false, he also blindly insists upon a
mad-cow with Alzheimer’s, Parkinson’s, and Lou Gehrig’s disease. His specific
allegations have been clearly refuted by Centers for Disease Countrol and
Prevention scientists in the journal Neurology.
snip...
who are these people ‘The Center For Consumer Freedom’ ?
see full comment on TSS ;
Sunday, September 25, 2011
Mad Cow Scaremongers
Mad Cow Scaremongers by Terry S. Singeltary Sr. a review of the TSE prion
agent 2003-2011
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
EFSA and the European Centre for Disease Prevention and Control (ECDC)
recently delivered a scientific opinion on any possible epidemiological or
molecular association between TSEs in animals and humans (EFSA Panel on
Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical
BSE prions as the only TSE agents demonstrated to be zoonotic so far but the
possibility that a small proportion of human cases so far classified as
"sporadic" CJD are of zoonotic origin could not be excluded. Moreover,
transmission experiments to non-human primates suggest that some TSE agents in
addition to Classical BSE prions in cattle (namely L-type Atypical BSE,
Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic
wasting disease (CWD) agents) might have zoonotic potential.
snip...
Thursday, August 12, 2010
Seven main threats for the future linked to prions
First threat
The TSE road map defining the evolution of European policy for protection
against prion diseases is based on a certain numbers of hypotheses some of which
may turn out to be erroneous. In particular, a form of BSE (called atypical
Bovine Spongiform Encephalopathy), recently identified by systematic testing in
aged cattle without clinical signs, may be the origin of classical BSE and thus
potentially constitute a reservoir, which may be impossible to eradicate if a
sporadic origin is confirmed.
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases
constitute an unforeseen first threat that could sharply modify the European
approach to prion diseases.
Second threat
snip...
Monday, January 14, 2013
Gambetti et al USA Prion Unit change another highly suspect USA mad cow
victim to another fake name i.e. sporadic FFI at age 16 CJD Foundation goes
along with this BSe
Monday, December 31, 2012
Creutzfeldt Jakob Disease and Human TSE Prion Disease in Washington State,
2006–2011-2012
Saturday, December 29, 2012
MAD COW USA HUMAN TSE PRION DISEASE DECEMBER 29 2012 CJD CASE LAB REPORT
Tuesday, December 25, 2012
CREUTZFELDT JAKOB TSE PRION DISEASE HUMANS END OF YEAR REVIEW DECEMBER 25,
2012
Friday, November 23, 2012
sporadic Creutzfeldt-Jakob Disease update As at 5th November 2012 UK, USA,
AND CANADA
Letters
JAMA. 2001;285(6):733-734. doi: 10.1001/jama.285.6.733
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Terry S. Singeltary, Sr Bacliff, Tex
Since this article does not have an abstract, we have provided the first
150 words of the full text.
KEYWORDS: creutzfeldt-jakob disease, diagnosis.
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.
References 1. Gibbons RV, Holman RC, Belay ED, Schonberger LB.
Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA.
2000;284:2322-2323.
Published March 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease
in the United States
Terry S. Singeltary, retired (medically)
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?
Published March 26, 2003
THE PATHOLOGICAL PROTEIN
BY Philip Yam Yam Philip Yam News Editor Scientific American www.sciam.com
Answering critics like Terry Singeltary, who feels that the U.S. under-
counts CJD, Schonberger conceded that the current surveillance system has errors
but stated that most of the errors will be confined to the older population.
CHAPTER 14
Laying Odds
Are prion diseases more prevalent than we thought?
Researchers and government officials badly underestimated the threat that
mad cow disease posed when it first appeared in Britain. They didn't think
bovine spongiform encephalopathy was a zoonosis-an animal disease that can
sicken people. The 1996 news that BSE could infect humans with a new form of
Creutzfeldt-Jakob disease stunned the world. It also got some biomedical
researchers wondering whether sporadic CJD may really be a manifestation of a
zoonotic sickness. Might it be caused by the ingestion of prions, as variant CJD
is?
Revisiting Sporadic CJD
It's not hard to get Terry Singeltary going. "I have my conspiracy
theories," admitted the 49-year-old Texan.1 Singeltary is probably the nation's
most relentless consumer advocate when it comes to issues in prion diseases. He
has helped families learn about the sickness and coordinated efforts with
support groups such as CJD Voice and the CJD Foundation. He has also connected
with others who are critical of the American way of handling the threat of prion
diseases. Such critics include Consumers Union's Michael Hansen, journalist John
Stauber, and Thomas Pringle, who used to run the voluminous www.madcow. org Web
site. These three lend their expertise to newspaper and magazine stories about
prion diseases, and they usually argue that prions represent more of a threat
than people realize, and that the government has responded poorly to the dangers
because it is more concerned about protecting the beef industry than people's
health.
Singeltary has similar inclinations. ...
snip...
THE PATHOLOGICAL PROTEIN
Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9
June 2003 BY Philip Yam
CHAPTER 14 LAYING ODDS
Answering critics like Terry Singeltary, who feels that the U.S. under-
counts CJD, Schonberger conceded that the current surveillance system has errors
but stated that most of the errors will be confined to the older population.
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North
America update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember,
the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been
documented in North America, along with the typical scrapie's, and atypical
Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these
TSE in different species have been rendered and fed to food producing animals
for humans and animals in North America (TSE in cats and dogs ?), and that the
trading of these TSEs via animals and products via the USA and Canada has been
immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances
and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD
only theory in 2009. With all the science to date refuting it, to continue to
validate this old myth, will only spread this TSE agent through a multitude of
potential routes and sources i.e. consumption, medical i.e., surgical, blood,
dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and
the urgent need to make all human TSE in the USA a reportable disease, in every
state, of every age group, and to make this mandatory immediately without
further delay. The ramifications of not doing so will only allow this agent to
spread further in the medical, dental, surgical arena's. Restricting the
reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO
age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge,
Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al
and many more, that the world of TSE Transmissible Spongiform Encephalopathy is
far from an exact science, but there is enough proven science to date that this
myth should be put to rest once and for all, and that we move forward with a new
classification for human and animal TSE that would properly identify the
infected species, the source species, and then the route.
Article
Human Prion Diseases in the United States
Robert C. Holman mail, Ermias D. Belay, Krista Y. Christensen, Ryan A.
Maddox, Arialdi M. Minino, Arianne M. Folkema, Dana L. Haberling, Teresa A.
Hammett, Kenneth D. Kochanek, James J. Sejvar, Lawrence B. Schonberger
CJD Singeltary submission to PLOS ;
No competing interests declared.
new link url ;
Wednesday, May 19, 2010
Molecular, Biochemical and Genetic Characteristics of BSE in Canada
>>> The occurrence of atypical cases of BSE in countries such as
Canada with low BSE prevalence and transmission risk argues for the occurrence
of sporadic forms of BSE worldwide. <<<
RE-Molecular, Biochemical and Genetic Characteristics of BSE in Canada
Posted by flounder on 19 May 2010 at 21:21 GMT
Greetings,
>>> The occurrence of atypical cases of BSE in countries such as
Canada with low BSE prevalence and transmission risk argues for the occurrence
of sporadic forms of BSE worldwide. <<<
In my opinion ;
THE statement above is about as non-scientific as a statement can be. There
is no proof what-so-ever that any of the atypical BSE cases or atypical scrapie
cases anywhere on the globe was a spontaneous case without any route and source
of the TSE agent. This is a myth. The USDA and the OIE are trying to make the
atypical BSE cases and they have already made the atypical Scrapie cases a legal
trading commodity, without any transmission studies first confirming that in
fact these atypical TSE will not transmit via feed. I suppose it is a human
transmission study in progress. IT's like what happened in England with c-BSE
and the transmission to humans via nvCJD never happened to the OIE and the USDA.
Canada does not have a low prevalence of BSE either, they have a high
prevalence. WHO knows about North America ? it's just that the U.S.A. try's much
harder at concealing cases of mad cow disease. THIS was proven with the first
stumbling and staggering mad cow in Texas, that was Wisk away to be rendered
without any test at all. Then, you had the second case of mad cow disease that
the USDA et al was almost as successful with as the first one, but the O.I.G.
stepped in and demanded testing over seas, this after many scientist around the
globe spoke out. Finally, after an act of Congress, the second case of mad cow
disease in Texas was confirmed. all this was done for a reason, and that reason
was the OIE USDA BSE MRR policy. Again, This study reeks of TRADE policy
wrangling. There is NO proof that the atypical TSE are spontaneous. please show
me these transmission studies ? on the other hand, we now know that the L-type
atypical BSE is much more virulent than the typical C-BSE, and we now know that
the H-type atypical BSE will transmit to humans. WHY can it not be that these
atypical cases are simply from feed that had different strains of TSE ? WHY is
it that no one will comment on the studies that was suppose to show infectivity
of tissues from atypical BSE ? WHY is it I had to file a FOIA on that issue?
L-type atypical BSE (BASE) is more virulent than classical BSE, has a
lymphotropic phenotype, and displays a modest transmission barrier in our
humanized mice. BSE-H is also transmissible in our humanized Tg mice. SEE
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw
Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1
et al 2009 ;
Atypical BSE, BSE, and other human and animal TSE in North America Update
October 19, 2009
snip...
I ask Professor Kong ;
Thursday, December 04, 2008 3:37 PM
Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform
Encephalopathies (BSE): Public Health Risk Assessment
IS the h-BSE more virulent than typical BSE as well, or the same as cBSE,
or less virulent than cBSE? just curious.....
Professor Kong reply ;
.....snip
As to the H-BSE, we do not have sufficient data to say one way or another,
but we have found that H-BSE can infect humans. I hope we could publish these
data once the study is complete. Thanks for your interest.
Best regards, Qingzhong Kong, PhD Associate Professor Department of
Pathology Case Western Reserve University Cleveland, OH 44106 USA
P.4.23 Transmission of atypical BSE in humanized mouse models
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw
Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1
1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale,
Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research
Institute, Poland; 5Kansas State University (Previously at USDA National Animal
Disease Center), USA
Background: Classical BSE is a world-wide prion disease in cattle, and the
classical BSE strain (BSE-C) has led to over 200 cases of clinical human
infection (variant CJD). Atypical BSE cases have been discovered in three
continents since 2004; they include the L-type (also named BASE), the H-type,
and the first reported case of naturally occurring BSE with mutated bovine PRNP
(termed BSE-M). The public health risks posed by atypical BSE were argely
undefined.
Objectives: To investigate these atypical BSE types in terms of their
transmissibility and phenotypes in humanized mice.
Methods: Transgenic mice expressing human PrP were inoculated with several
classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the
transmission rate, incubation time, characteristics and distribution of PrPSc,
symptoms, and histopathology were or will be examined and compared.
Results: Sixty percent of BASE-inoculated humanized mice became infected
with minimal spongiosis and an average incubation time of 20-22 months, whereas
only one of the C-type BSE-inoculated mice developed prion disease after more
than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse
brains was biochemically different from bovine BASE or sCJD. PrPSc was also
detected in the spleen of 22% of BASE-infected humanized mice, but not in those
infected with sCJD. Secondary transmission of BASE in the humanized mice led to
a small reduction in incubation time. The atypical BSE-H strain is also
transmissible with distinct phenotypes in the humanized mice, but no BSE-M
transmission has been observed so far.
Discussion: Our results demonstrate that BASE is more virulent than
classical BSE, has a lymphotropic phenotype, and displays a modest transmission
barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg
mice. The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
SNIP...
Thursday, February 14, 2013
The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and
TSE prion disease
with kindest regards,
terry
MOM RIP 12/14/97 confirmed Heidenhain Variant Creutzfeldt Jakob Disease and
her MOM and Brother died with Alzheimer’s...I can’t wait to see what
happens...not.
