Thursday, July 12, 2012

Potential contribution of exosomes to the prion-like propagation of lesions in Alzheimer’s disease

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


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