Potential contribution of exosomes to the prion-like propagation of
lesions in Alzheimer’s disease
Valérie Vingtdeux1, Nicolas Sergeant2,3* and Luc Buée2,3* 1 Litwin-Zucker
Research Center for the Study of Alzheimer’s Disease, The Feinstein Institute
for Medical Research, North Shore-Long Island Jewish, Manhasset, NY, USA 2 UMR
837, Institute National pour la Santé et la Recherche Medical, Alzheimer and
Tauopathies, Lille, France 3 Faculty of Medicine, Jean-Pierre Aubert Research
Centre, Institute of Predictive Medicine and Therapeutic Research, Université
Lille Nord de France, UDSL, Place de Verdun, Lille, France
Since the discovery of prion diseases, the concept has emerged that a
protein could be a transmissible pathogen. As such, this transmissible pathogen
agent can transfer its pathological mis-folded shape to the same but normally
folded protein thus leading to the propagation of a disease. This idea is now
extrapolated to several neurological diseases associated with protein
mis-folding and aggregation, such as Alzheimer’s disease (AD). AD is a slowly
developing dementing disease characterized by the coexistence of two types of
lesions: the parenchymal amyloid deposits and the intraneuronal neurofibrillary
tangles (NFT). Amyloid deposits are composed of amyloid-beta peptides that
derive from sequential cleavages of its precursor named amyloid protein
precursor. NFT are characterized by intraneuronal aggregation of abnormally
modified microtubule-associated Tau proteins. A synergistic relationship between
the two lesions may trigger the progression of the disease. Thus, starting in
the medial temporal lobe and slowly progressing through temporal, frontal,
parietal, and occipital cortex, the spreading of NFT is well correlated with
clinical expression of the disease and likely follows cortico-cortical neuronal
circuitry. However, little is known about the mechanism driving the
spatiotemporal propagation of these lesions ultimately leading to the disease. A
growing number of studies suggest that amyloid deposits and NFT are resulting
from a prion-like spreading. In the present chapter, we will develop the current
hypotheses regarding the molecular and cellular mechanisms driving the
development and spreading of AD lesions from the window of multivesicular
endosomes/bodies and exosomes.
Keywords: Alzheimer’s disease, tauopathies, multivesicular bodies,
exosomes, amyloid precursor protein, microtubule-associated tau protein
Citation: Vingtdeux V, Sergeant N and Buée L (2012) Potential contribution
of exosomes to the prion-like propagation of lesions in Alzheimer’s disease.
Front. Physio. 3:229. doi: 10.3389/fphys.2012.00229
Received: 16 January 2012; Accepted: 06 June 2012; Published online: 05
July 2012.
Edited by: Claudia Verderio, CNR Institute of Neuroscience, Italy
Reviewed by: Lawrence Rajendran, University Zurich, Switzerland Andrew
Hill, The University of Melbourne, Australia Pascal Kienlen-Campard, Université
Catholique de Louvain, Belgium Copyright:© 2012 Sergeant, Buee and Vingtdeux.
This is an open-access article distributed under the terms of the Creative
Commons Attribution Non Commercial License, which permits non-commercial use,
distribution, and reproduction in other forums, provided the original authors
and source are credited.
*Correspondence: Nicolas Sergeant and Luc Buée, UMR 837, Institute National
Pour la Santé et la Recherche Medical, Alzheimer and Tauopathies, Centre de
Recherches Jean-Pierre Aubert, Faculté de Médecine Pole Recherche, Place de
Verdun, F-59045 Lille, France. e-mail: nicolas.sergeant@inserm.fr; luc.buee@inserm.fr
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
From: Terry S. Singeltary Sr.
Sent: Wednesday, May 16, 2012 3:29 PM
To: BSE-L@LISTS.AEGEE.ORG
Subject: [BSE-L] Alzheimer’s disease and Transmissible Spongiform
Encephalopathy prion disease, Iatrogenic, what if ?
Proposal ID: 29403
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Background
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease
have both been around a long time, and was discovered in or around the same time
frame, early 1900’s. Both disease, and it’s variants, in many cases are merely
names of the people that first discovered them. Both diseases are incurable and
debilitating brain disease, that are in the end, 100% fatal, with the
incubation/clinical period of the Alzheimer’s disease being longer than the TSE
prion disease. Symptoms are very similar, and pathology is very similar. I
propose that Alzheimer’s is a TSE disease of low dose, slow, and long incubation
disease, and that Alzheimer’s is Transmissible, and is a threat to the public
via the many Iatrogenic routes and sources. It was said long ago that the only
thing that disputes this, is Alzheimer’s disease transmissibility, or the lack
of. today, there is enough documented science (some confidential), that shows
that indeed Alzheimer’s is transmissible. The risk factor for friendly fire, and
or the pass-it-forward mode i.e. Iatrogenic transmission is a real threat, and
one that needs to be addressed immediately.
Methods
Through years of research, as a layperson, of peer review journals,
transmission studies, and observations of loved ones and friends that have died
from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant
Creutzfelt Jakob Disease CJD.
Results
The likelihood of many victims of Alzheimer’s disease from the many
different Iatrogenic routes and modes of transmission as with the TSE prion
disease. TSE prion disease survives ashing to 600 degrees celsius, that’s around
1112 degrees farenheit. you cannot cook the TSE prion disease out of meat. you
can take the ash and mix it with saline and inject that ash into a mouse, and
the mouse will go down with TSE. Prion Infected Meat-and-Bone Meal Is Still
Infectious after Biodiesel Production as well. the TSE prion agent also survives
Simulated Wastewater Treatment Processes. IN fact, you should also know that the
TSE Prion agent will survive in the environment for years, if not decades. you
can bury it and it will not go away. TSE prion agent is capable of infected your
water table i.e. Detection of protease-resistant cervid prion protein in water
from a CWD-endemic area. it’s not your ordinary pathogen you can just cook it
out and be done with. that’s what’s so worrisome about Iatrogenic mode of
transmission, a simple autoclave will not kill this TSE prion agent.
Conclusions
There should be a Global Congressional Science round table event (one of
scientist and doctors et al only, NO CORPORATE, POLITICIANS ALLOWED) set up
immediately to address these concerns from the many potential routes and sources
of the TSE prion disease, including Alzheimer’s disease, and a emergency global
doctrine put into effect to help combat the spread of Alzheimer’s disease via
the medical, surgical, dental, tissue, and blood arena’s. All human and animal
TSE prion disease, including Alzheimer’s should be made reportable in every
state, and Internationally, WITH NO age restrictions. Until a proven method of
decontamination and autoclaving is proven, and put forth in use universally, in
all hospitals and medical, surgical arena’s, or the TSE prion agent will
continue to spread. IF we wait until science and corporate politicians wait
until politics let science _prove_ this once and for all, and set forth
regulations there from, we will all be exposed to the TSE Prion agents, if that
has not happened already. what’s the use of science progressing human life to
the century mark, if your brain does not work?
combined cannot exceed 350 Words
shortened to proper word count ;
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Background
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease
have both been around a long time, and was discovered in or around the same time
frame, early 1900’s. Both diseases are incurable and debilitating brain disease,
that are in the end, 100% fatal, with the incubation/clinical period of the
Alzheimer’s disease being longer (most of the time) than the TSE prion disease.
Symptoms are very similar, and pathology is very similar.
Methods
Through years of research, as a layperson, of peer review journals,
transmission studies, and observations of loved ones and friends that have died
from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant
Creutzfelt Jakob Disease CJD.
Results
I propose that Alzheimer’s is a TSE disease of low dose, slow, and long
incubation disease, and that Alzheimer’s is Transmissible, and is a threat to
the public via the many Iatrogenic routes and sources. It was said long ago that
the only thing that disputes this, is Alzheimer’s disease transmissibility, or
the lack of. The likelihood of many victims of Alzheimer’s disease from the many
different Iatrogenic routes and modes of transmission as with the TSE prion
disease.
Conclusions
There should be a Global Congressional Science round table event set up
immediately to address these concerns from the many potential routes and sources
of the TSE prion disease, including Alzheimer’s disease, and a emergency global
doctrine put into effect to help combat the spread of Alzheimer’s disease via
the medical, surgical, dental, tissue, and blood arena’s. All human and animal
TSE prion disease, including Alzheimer’s should be made reportable in every
state, and Internationally, WITH NO age restrictions. Until a proven method of
decontamination and autoclaving is proven, and put forth in use universally, in
all hospitals and medical, surgical arena’s, or the TSE prion agent will
continue to spread. IF we wait until science and corporate politicians wait
until politics lets science _prove_ this once and for all, and set forth
regulations there from, we will all be exposed to the TSE Prion agents, if that
has not happened already.
end...tss
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
source references
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.
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
Wednesday, January 5, 2011
ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions
David W. Colby1,* and Stanley B. Prusiner1,2
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, September 21, 2011
PrioNet Canada researchers in Vancouver confirm prion-like properties in
Amyotrophic Lateral Sclerosis (ALS)
snip...end
Thank You for accepting my submission
# 29403, Alzheimer’s disease and Transmissible Spongiform Encephalopathy
prion disease, Iatrogenic, what if ? and the opportunity to present it, at the
Alzheimer’s Association International Conference 2012 (AAIC), as a poster
presentation. However, with great sadness, I must regretfully decline the
invitation due to a medical reasons, and traveling to Canada, of which is not
possible. ...
Thank You,
With Kindest Regards,
I am sincerely,
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
flounder9@verizon.net
From:
Sent: Saturday, April 07, 2012 8:20 PM
To: Terry S. Singeltary Sr.
Subject: RE: re-submission
Dear Terry,
Yes, your proposal was accepted as a poster presentation. Please decline
the invitation if appropriate.
Best Regards,
______________________________________
Alzheimer’s Association – National Office
225 North Michigan Avenue – Floor 17
Chicago, Illinois 60601
=============snip...end...source reference...# 29403==========
Wednesday, May 16, 2012
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Proposal ID: 29403
TSS
==============JUNE 2012 UPDATE TSE USA=====================
Wednesday, June 27, 2012
First US BSE Case Since 2006 Underscores Need for Vigilance
Neurology Today 21 June 2012
Tuesday, June 26, 2012
Creutzfeldt Jakob Disease Human TSE report update North America, Canada,
Mexico, and USDA PRION UNIT as of May 18, 2012
type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the
rise in Canada and the USA
MOM DOD 12/14/97 CONFIRMED HVCJD I.E. THE HEIDENHAIN VARIANT OF CREUTZFELDT
JAKOB DISEASE...TSS
Tuesday, July 29, 2008
Heidenhain Variant Creutzfeldt Jakob Disease Case Report
FINAL AUTOPSY DIAGNOSIS
I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.
SKROLL down a bit for Mom's autopsy of hvCJD. ...
mom, I’m still here damn’t. ...
TSS
LAYPERSON
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
