TECHNICAL REPORT Annual report of the Scientific Network on BSE-TSE 20131
European Food Safety Authority2, 3 European Food Safety Authority (EFSA), Parma,
Italy
EFSA supporting publication 2013:EN-532 7
Scientific update on the potential for transmissibility of non-prion
protein misfolding diseases
The representative from Austria updated the participants on scientific
issues related to the prion-like behaviour of altered proteins (‘prionoids’).
The state of the art of experimental and epidemiological evidence on the
potential for transmissibility of non-TSE protein misfolding diseases was
presented. Experimental evidence shows that there are proteins (e.g. Abeta
amyloid, tau, alpha-synuclein) that can behave in a similar way to the prion
protein in terms of in-vivo propagation when experimentally inoculated animal
models. There is no epidemiological evidence that human to human transmission
has occurred in cases other than prion disorders. Still, it is acknowledged that
the epidemiological investigation of the occurrence of this hypothetical
phenomenon is not straight forward.
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 ;
Nature Immunology | Article
The adaptor ASC has extracellular and 'prionoid' activities that propagate
inflammation
Bernardo S Franklin, Lukas Bossaller, Dominic De Nardo, Jacqueline M
Ratter, Andrea Stutz, Gudrun Engels, Christoph Brenker, Mark Nordhoff, Sandra R
Mirandola, Ashraf Al-Amoudi, Matthew S Mangan, Sebastian Zimmer, Brian G Monks,
Martin Fricke, Reinhold E Schmidt, Terje Espevik, Bernadette Jones, Andrew G
Jarnicki, Philip M Hansbro, Patricia Busto, Ann Marshak-Rothstein, Simone
Hornemann, Adriano Aguzzi, Wolfgang Kastenmüller & Eicke Latz Affiliations
Contributions Corresponding author Nature Immunology 15, 727–737 (2014)
doi:10.1038/ni.2913 Received 31 March 2014 Accepted 01 May 2014 Published online
22 June 2014
Abstract
Microbes or danger signals trigger inflammasome sensors, which induce
polymerization of the adaptor ASC and the assembly of ASC specks. ASC specks
recruit and activate caspase-1, which induces maturation of the cytokine
interleukin 1β (IL-1β) and pyroptotic cell death. Here we found that after
pyroptosis, ASC specks accumulated in the extracellular space, where they
promoted further maturation of IL-1β. In addition, phagocytosis of ASC specks by
macrophages induced lysosomal damage and nucleation of soluble ASC, as well as
activation of IL-1β in recipient cells. ASC specks appeared in bodily fluids
from inflamed tissues, and autoantibodies to ASC specks developed in patients
and mice with autoimmune pathologies. Together these findings reveal
extracellular functions of ASC specks and a previously unknown form of
cell-to-cell communication.
This low rate of transmission may be due to low levels of PrPres in the
brain homogenates that were inoculated, or it could be that the PrP genotype
plays a role in transmission of disease.
Prion disease propagation involves the aggregation of abnormal PrP that
acts as a template for further aggregation within the brain, a process termed
seeding (21,22). The spread of PrP within the brain appears to occur in
cell-to-cell fashion in well-defined neuroanatomic pathways (23), the mechanisms
of which are yet to be elucidated despite extensive studies. Prion diseases have
the potential to be transmissible between persons, a fact that raises public
health concerns, particularly regarding vCJD. Assessing the risk for
transmission is a challenge because of the varied nature of prion diseases and
conflicting evidence over the mechanisms of transmission. Risk assessment is
made even more complicated by the existence of prion disease models in which
negligible amounts of PrPres are associated with high infectivity titers in vivo
(24) and also of models in which PrPres in the form of amyloid plaques develops
in the absence of clinical disease or spongiform changes (25).
It could be argued that the observation of small plaque-like amyloid
deposits in the brains of mice with no neurologic signs of disease after the
inoculation of brain homogenates prepared from patients with VPSPr does not
indicate disease transmission. Instead, the deposits could indicate an amyloid
seeding phenomenon akin to that observed following the experimental inoculation
of primates with brain tissue from patients with Alzheimer disease (26). In
those experiments, amyloid β seeding occurred in the primate brain in the
absence of any clinical signs. Precedence of this phenomenon in prion disease
has been set by Piccardo et al. (27), who showed similar results in a mouse
model system of prion disease transmission. However, in our study, the brain of
1 mouse exhibited intensely stained, small, round granules within the
hippocampus in addition to the plaque-like deposits (Figure 4). These small
granules are reminiscent of the microplaques found in brain tissue of humans
with VPSPr (4,5). Furthermore, with 4 PrP antibodies, the microplaque deposits
in the mouse brain showed the same pattern of differential immunoreactivity as
that in the brain of patients with VPSPr (5,6,17). Moreover astrocytosis in the
vicinity of the microplaques was also observed in this mouse (Figure 5). This
type of astrocytic response is observed in all our model systems of
transmissible prion disease, but is absent from the nontransmissible forms of
PrP (i.e., amyloid plaques in absence of clinical disease), suggesting that this
single mouse may represent a transmission of infection rather than a consequence
of seeding of inoculum (25,28). Second passage in the same mouse line will be
required to prove this interpretation, but such a study will take an additional
3 years to complete. Although understanding the mechanisms of transmission is an
interesting facet of this study, our primary finding is that VPSPr is capable of
transmission to transgenic mice expressing PrP, albeit at extremely low levels
compared with those of other transmissible prion diseases (e.g., sCJD and vCJD).
We demonstrate that VPSPr is a disease with biological properties distinct from
those of sCJD and with a limited, but not negligible, potential for infectivity.
These results demonstrate the importance of continuing surveillance to fully
uncover the growing spectrum of human prion diseases.
>>> We demonstrate that VPSPr is a disease with biological
properties distinct from those of sCJD and with a limited, but not negligible,
potential for infectivity. These results demonstrate the importance of
continuing surveillance to fully uncover the growing spectrum of human prion
diseases.<<<
Friday, January 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type
prion disease, what it ???
Monday, November 3, 2014
*** The prion protein protease sensitivity, stability and seeding activity
in variably protease sensitive prionopathy brain tissue suggests molecular
overlaps with sporadic Creutzfeldt-Jakob disease
Sunday, November 23, 2014
Transmission Characteristics of Variably Protease-Sensitive Prionopathy
* We concluded that VPSPr is transmissible; thus, it is an authentic prion
disease.
Sunday, November 23, 2014
Transmission Characteristics of Variably Protease-Sensitive Prionopathy
* We concluded that VPSPr is transmissible; thus, it is an authentic prion
disease.
Friday, January 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type
prion disease, what it ???
Monday, November 17, 2014
Prion-like transmission and spreading of tau pathology
Saturday, February 16, 2013
Prions, prionoids and pathogenic proteins in Alzheimer disease
Monday, September 26, 2011
Variably Protease-Sensitive Prionopathy, Prionpathy, Prionopathy, FFI, GSS,
gCJD, hvCJD, sCJD, TSE, PRION, update 2011
Are some commoner types of neurodegenerative disease (including
Alzheimer's disease and Parkinson's disease) also transmissible? Some recent
scientific research has suggested this possibility
Wednesday, September 21, 2011
PrioNet Canada researchers in Vancouver confirm prion-like properties in
Amyotrophic Lateral Sclerosis (ALS)
Researchers’ Discovery May Revolutionize Treatment of ALS
Friday, September 3, 2010
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's,
Prionoids, Prionpathy, Prionopathy, TSE
Sunday, November 23, 2014
Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in
June 2014 confirmed as USA case NOT European
‘’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.’’
Friday, December 5, 2014
SPECIAL ALERT The OIE recommends strengthening animal disease surveillance
worldwide
OIE BSE TSE PRION AKA MAD COW DISEASE ?
‘’the silence was deafening’’ ...tss
Saturday, December 6, 2014
Detection of Bovine Central Nervous System Tissues in Rendered Animal
By-Products by One-Step Real-Time Reverse Transcription PCR Assay
TSS
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