Canadian scientists get $2.9 million to prevent Prion Disease outbreaks; Montana FWP approves Wolf hunt quotas; Arizona’s Coconino County targets Gray Foxes for Rabies vaccination; West Nile Virus reports from New York, and Ohio; and Rabies reports from California, Georgia, Maine, Maryland, New Jersey, New York, Pennsylvania, Texas, and Virginia.

Bull Elk. Photo by Mongo. PD. Wikimedia Commons.

Canada 07/13/11 prionetcanada.ca: Press Release – Collaborative research groups at nine different universities, involving 55 different investigators across Canada, are poised to make significant advances in the understanding of prion and prion-like diseases in humans and animals.

Captive elk with chronic wasting disease

These include the development of an oral vaccine to help stop the spread of chronic wasting disease (CWD) in wild deer and elk populations and novel approaches to treat human neurodegenerative disorders like ALS (Lou Gehrig’s disease), Alzheimer’s and Parkinson’s diseases, thanks to $2.9 million in funding announced by PrioNet Canada.  The goal of the funding which supports 11 projects is two-fold, explains Dr. Neil Cashman, Scientific Director of PrioNet Canada, one of Canada’s Network of Centres of Excellence. “By working with our partners, we aim to continue to protect Canada against classical prion diseases like chronic wasting disease and mad cow disease (bovine spongiform encephalopathy or BSE), and we’re also providing benefit to Canadians through the development of innovative therapeutics to treat neurodegenerative diseases like Alzheimer’s, Parkinson’s and ALS.”

Sheep with scrapie.

The researchers will use the funds to better understand the biology of prion disease, to develop strategies to manage prion disease outbreaks and minimize the impacts, and to apply learnings of prion diseases to the treatment of human neurodegenerative disorders. Prion diseases are fatal, infectious and transmissible diseases of humans and animals associated with a ‘sponge-like’ degeneration of brain tissue. In animals, the most common prion diseases include BSE, scrapie in sheep and goats, and CWD in deer and elk. In 2003, Canada’s beef and related industries were faced with worldwide closing of trade after a domestic case of BSE was found in Alberta. Canada’s economic loss stemming from this event is estimated at more than $6 billion. Some examples of prion diseases in humans include fatal and sporadic familial insomnia, Creutzfeldt-Jakob disease (CJD) and its many varieties, and Kuru. Some examples of the ground-breaking work supported by PrioNet’s recent funding include:

Dr. Neil Cashman

Immunotherapies to treat ALS: Five PrioNet researchers at the University of British Columbia, University of Alberta and University of Toronto are focusing on a newly-recognized molecular mechanism of ALS, a misfolded protein called SOD-1. By identifying the parts of the protein that are exposed when it is misfolded in disease, researchers are able to design immunotherapies that can target those areas, interrupting the slow progression of paralysis and eventual death characterized by the disorder. Two animal models have already demonstrated responsiveness to the new immunotherapies and work is now underway to develop a therapy for humans. “We are hoping these discoveries could prove to be a magic bullet for ALS,” said Dr. Cashman, who serves as principal investigator for the multi-disciplinary research team.

Dr. Scott Napper

Oral vaccine to control chronic wasting disease in the wild: Prion diseases like chronic wasting disease are continuing to spread throughout the Canadian prairie’s wild deer and elk populations and ten PrioNet researchers in Saskatoon and British Columbia are working on an oral vaccine to stop the spread. “The danger is that prion diseases are evolving and new strains are emerging,” noted Dr. Scott Napper, a Research Scientist with the Vaccine and Infectious Disease Organization in Saskatoon and principal investigator on the project. Dr. Napper’s group is focusing on an oral vaccine that can withstand extreme temperatures and will effectively attract elk and deer in the wild. Similar oral vaccines are already used to control rabies in Eastern Canada, where food packets containing the vaccine are widely distributed for consumption by fox and raccoon populations.

Dr. Ellen Goddard

Framework to minimize the impact of chronic wasting disease: Principal investigator Dr. Ellen Goddard from the University of Alberta along with nine co-investigators are working to identify the risk factors associated with chronic wasting disease in wild deer and elk populations, how they can be managed and what public policy recommendations should be put in place to try and mitigate the effects. The primary goal is to monitor the many unknowns that remain about the impact of CWD in the wild, such as the potential risk to hunters who consume infected animals and the potential interface between wild and domestic animals. “The risk management framework around BSE showed that even though countries were aware of the disease in their cattle, they completely underestimated the economic impact and the public response,” notes Dr. Goddard. “We’re doing the work ahead of the game while CWD is still manageable and while effective policies can be put into place to control it, to help anticipate and prevent the impacts.”

Dr. Christoph Borchers

Understanding ‘good versus bad’ prions in order to develop drugs: The first step to designing drugs to treat prion and prion-like diseases is to understand how prion proteins change shape when they become “misfolded” in disease. Dr. Christoph Borchers, a Professor in the Department of Biochemistry and Microbiology and Director of the University of Victoria-Genome BC Proteomics Centre is collaborating with researchers from the University of Alberta and University of Western Ontario to characterize the changes that occur to the three-dimensional structure of prion fibrils (small, nerve-like fibres) as well as the molecular mechanisms that lead to those changes. Using a combination of protein chemistry and mass spectrometry, they are
working to explain what occurs when a ‘good’ prion protein changes to a ‘bad’ one during disease development. The information is crucial to designing drugs that can interfere with those changes, effectively curbing the spread of prion and prion-like diseases.

About PrioNet Canada (www.prionetcanada.ca)
One of Canada’s Networks of Centres of Excellence, PrioNet Canada is a pan-Canadian research network that is developing strategies to help solve the food, health safety, and socioeconomic problems associated with prion diseases. The network brings together academia, industry, and public sector partners through its multidisciplinary research projects, training programs, events, and commercialization activities to help derive maximum socioeconomic benefits for Canadians. PrioNet is hosted by the University of British Columbia and the Vancouver Coastal Health Research Institute in Vancouver.

Montana 07/14/11mt.gov: Press Release – Montana’s Fish, Wildlife & Parks Commission today approved a wolf hunting season for 2011 that creates 14 wolf management units and an overall harvest quota of 220 wolves. “The approved hunting season is very similar to the one considered last year,” said Ken McDonald, FWP’s chief of wildlife. “It’s based on wildlife science and we believe it’s properly balanced. Our management objective is very clear: we must maintain a viable and connected wolf population as we aim to reduce impacts on Montana’s wildlife and livestock. With the ability to manage wolves as we do all other wildlife in Montana we’re confident we can meet those expectations.” For the upcoming seasons, hunters will have the opportunity to hunt for 220 wolves in 14 WMUs that are generally situated in the western portion of Montana. A new WMU in the Bitterroot Valley was added to an area where wolves appear to be contributing to a significant drop in the elk population. (For complete news release go to http://fwp.mt.gov/news/newsReleases/headlines/nr_3966.html )

Arizona 07/14/11 myfoxphoenix.com: Coconino County health officials are asking cat and dog owners to keep their pets leashed or confined this year while area wildlife is vaccinated against rabies. The quarantine lasts from August 1 – 12. That’s when county and federal workers and volunteers plan to distribute edible vaccine packets by hand in populated areas and by aircraft across a larger area that includes northeast Williams,
Mountainaire, Flagstaff and Winona. The primary targets for vaccination are gray foxes and this is the fifth such campaign in a decade. The quarantine is intended to prevent pets from eating the vaccines first. The vaccine bait packets aren’t supposed to be harmful to pets, but the Coconino County health department is advising people not to touch them.

New York 07/14/11 patch.com: by Ryan Bonner – The presence of the West Nile virus has been confirmed in mosquitoes in Patchogue, according to county health officials. It is the first confirmation of West Nile on Long Island this year. Three people in Suffolk and three in Nassau died in 2010 after being infected with the virus. No humans, horses or birds have tested positive for West Nile in Suffolk this year, the Suffolk County Department of Health Services (SCDHS) said in a press release. The mosquito sample in Patchogue that tested positive for the virus was collected on June 30.

Ohio 07/14/11 twinsburgbulletin.com: by Jeremy Nobile – The Summit County Health District has captured a mosquito carrying the West Nile virus in Twinsburg Township, though one health department official says there’s no cause for alarm. The bug was caught about two weeks ago in Liberty Park at 4175 East Aurora Road and tests in Columbus July 14 confirmed presence of the virus. Terry Tuttle, environmental health supervisor with the Summit County Health District, said it’s the fifth confirmed finding of the virus in Summit County this year — the other WNV-carrying insects were found in New Franklin, Cuyahoga Falls, Copley and Tallmadge. There were nine WNV-carrying mosquitoes caught in Summit County last year and only five in 2010 — but there were 15 in 2009. Tuttle also noted the last confirmed case of a human infected with WNV in the county was in 2002.

California 07/13/11 nctimes.com: by Chris Nichols – County health officials are warning the public not to touch dead animals after two boys in Vista turned in a dead but infected bat this past Sunday. The county is also urging the families of the unidentified boys, approximately 12 to 13 years old, to contact the county at 619-692-8499 to see if the boys were exposed to rabies. The boys brought the bat to the Petco store in Vista at 520 Hacienda Drive on Sunday, according to a county news release. The store immediately contacted authorities for help, the county said.

Georgia 07/13/11 patch.com: by Rodney Thrash – A raccoon that fought two Canton dogs has tested positive for rabies, health officials said. The dogs were vaccinated and will only require a 45-day quarantine, North Georgia Health District spokeswoman Jennifer King said in an email to Patch. There was no human exposure, she said. The positive test results came a week to the day that health officials said 11 Georgians were exposed to an unvaccinated rabid dog from Cherokee. Seven came from Cherokee County, three from Pickens County and one from Houston County. That case followed an incident in Ball Ground. On May 3, a rabid raccoon attacked a dog at a residence on Hightower Trail in Ball Ground. That dog was current on its vaccinations, too.

Maine 07/14/11 sunjournal.com: by Donna M. Perry – A raccoon tested positive for rabies after it attacked a pet cat resting on a deck Sunday at a residence on Spruce Mountain Road, Jay Animal Control Officer Larry Wright said Wednesday. It is the first case of rabies in Jay that Wright has seen this year, he said. The raccoon, which was euthanized, was handled by the Maine Warden Service and taken to the state laboratory for testing in Augusta. A representative of the lab called Wright Monday to tell him that the raccoon had rabies. The cat is under quarantine for six months or it needs to be euthanized because it did not have a rabies vaccination, Wright said.

Maryland 07/13/11 baltimorehealth.org: Press Release – The Baltimore City Health Department has confirmed a positive case of rabies in a domestic, short hair feline. The female cat was found July 7th on the side of the road in the 400 block of Kingston Road, just east of the Baltimore City/County line. The cat, a stray, was injured and immediately euthanized upon being taken to a veterinarian by a resident. The Health Department, at this time, is only aware of one human exposure the individual who attempted to rescue the cat. The individual is receiving medical attention. The last positive rabies case of a cat or dog in Baltimore City was in August 2008. Prior to that case, the last positive rabies case of a cat or dog was in 1986.

 New Jersey 07/14/11 patch.com: by Jennifer Bradshaw – The Middlesex County Health Department has issued a rabies advisory for the county after a stray cat tested positive for the virus on July 12. According to a release from the health department, the cat was discovered at a home in the vicinity of Lucille Court and Grandview Avenue in Piscataway. It was captured by animal control, brought to a veterinarian and euthanized, and tested for the virus.

New York 07/14/11 myfoxny.com:  The Westchester County Department of Health is issuing a rabies alert to residents who may have had contact with a rabid kitten near the entrance from Saw Mill River Road/Route 100 South to Route 9A North in Mount Pleasant, near the Briarcliff Manor border, prior to Wednesday, July 13. The cat was a stray, domestic short hair eight-week-old male that was solid black in color. The kitten was picked up by a passerby who brought it home on Tuesday, July 12 and then to a veterinarian, the next day, where it was submitted for rabies testing. Test results confirmed today that the cat was rabid. “Anyone who believes that they or a pet may have had contact with this cat should contact the Westchester County Department of Health immediately at (914) 813-5000 to assess the need for rabies treatment,” said Westchester County Acting Commissioner of Health, Dr. Cheryl Archbald. “Anyone bitten by a rabid animal, or having contact with its saliva, may need to receive immediate rabies vaccination.”

Pennsylvania 07/14/11 fultoncountynews.com: by Chanin Rotz-Mountz – The Pennsylvania Department of Agriculture confirmed last week a fox that was involved in a squabble with a dog in Brush Creek Township was indeed infected with the rabies virus.

Virginia 07/13/11 wavy.com: A fox found in the Moore Road area of Poquoson has tested positive for rabies. While preventable, rabies can be fatal. If you or your pet has come in contact with this animal, call the Peninsula Health District at (757) 594-7340.

Texas 07/13/11 fredericksburgstandard.com: Gillespie County’s fifth case of rabies in 2011 has been confirmed by the Texas Department of Health Services. The latest incident on June 27 occurred when, five hours after shooting a raccoon, a Gillespie resident noticed fluid on his hand when he picked up the animal by the tail. No risk to humans resulted in handling the raccoon, the TDHS Region 8 Zoonosis Control Office in Uvalde reported, before the animal was submitted for testing. The incident marks the second case of a rabid raccoon in the county this year after another case was reported in March.

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One response to “Canadian scientists get $2.9 million to prevent Prion Disease outbreaks; Montana FWP approves Wolf hunt quotas; Arizona’s Coconino County targets Gray Foxes for Rabies vaccination; West Nile Virus reports from New York, and Ohio; and Rabies reports from California, Georgia, Maine, Maryland, New Jersey, New York, Pennsylvania, Texas, and Virginia.

  1. GREAT NEWS FOR CANADA !!!

    what about the USA funding on prion related research ???

    USA

    All Other Emerging and Zoonotic Infectious Diseases CDC’s FY 2012 request of $52,658,000 for all other emerging and zoonotic infectious disease activities is a decrease of $13,607,000 below the FY 2010 level,

    which includes the elimination of Prion activities ($5,473,000),

    a reduction for other cross-cutting infectious disease activities, and administrative savings. These funds support a range of critical emerging and zoonotic infectious disease programs such Lyme Disease, Chronic Fatigue Syndrome, and Special Pathogens, as well as other activities described below.

    http://www.cdc.gov/fmo/topic/Budget%20Information/appropriations_budget_form_pdf/FY2012_CDC_CJ_Final.pdf

    ” the FY 2010 level, which includes the elimination of Prion activities ($5,473,000), ”

    USDA MAD COW PROBLEMS SOLVED $$$

    NOT !

    Saturday, June 25, 2011

    Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

    “BSE-L in North America may have existed for decades”

    http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html

    Sunday, June 26, 2011

    Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

    http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html

    Thursday, June 23, 2011

    Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

    http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html

    Wednesday, June 15, 2011

    Galveston, Texas – Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor

    http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html

    Thursday, June 2, 2011

    USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California

    http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html

    Monday, June 20, 2011 2011

    Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA

    http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html

    Monday, June 27, 2011

    Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease

    http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html

    Monday, November 30, 2009

    USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE

    http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html

    I strenuously urge the USDA and the OIE et al to revoke the exemption of the legal global trading of atypical Nor-98 scrapie TSE. …TSS

    Friday, February 11, 2011

    Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

    http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.html

    Thursday, November 18, 2010

    Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

    http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html

    Sunday, October 3, 2010

    Scrapie, Nor-98 atypical Scrapie, and BSE in sheep and goats North America, who’s looking ?

    http://nor-98.blogspot.com/2010/10/scrapie-nor-98-atypical-scrapie-and-bse.html

    Wednesday, July 06, 2011

    Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation

    (see tonnage of mad cow feed in commerce USA…tss)

    http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html

    Monday, June 27, 2011

    Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates

    http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.html

    Please see the following warning from CDC about prion TSE consumption in North America ;

    Thursday, May 26, 2011

    Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

    Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.

    http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html

    Tuesday, July 19, 2011

    Neuroanatomical Distribution of Disease-Associated Prion Protein in Cases of Bovine Spongiform Encephalopathy Detected by Fallen Stock Surveillance in Japan

    http://bse-atypical.blogspot.com/2011/07/neuroanatomical-distribution-of-disease.html

    Saturday, March 5, 2011

    MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

    http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html

    Oral.01: Changing Spectrum of Prions

    Stanley Prusiner

    University of California San Francisco, Institute for Neurodegenerative Diseases; San Francisco, CA USA

    Prions are self-propagating forms of proteins found in eukaryotes. Prions are created from benign, cellular precursor proteins by a posttranslational modification that is self-perpetuating. Often the prion form of the protein is aggregated and assembles into amyloid polymers. Prions can be inherited both genetically and epigenetically. In neurodegenerative diseases, the formation of prions is heritable through mutations in the gene encoding the cellular form of the prion protein. In fungi, the prion state is epigenetically transferred from mother to daughter cells.

    Historically, prions were confined to a small group of infectious CNS illnesses including Creutzfeldt-Jakob disease (CJD) and kuru of humans, scrapie of sheep, bovine spongiform encephalopathy, and chronic wasting disease of deer and elk. CJD can present as an infectious, inherited or sporadic illness. In all three manifestations of the disease, the cellular prion protein (PrPC) refolds into the disease-causing isoform (PrPSc). A truncated form of PrPSc readily polymerizes into amyloid fibrils and forms PrP amyloid plaques. Prion strains composed of different conformers of PrPScSc have been identified. Subsequently, prions were recognized in fungi and studied extensively using yeast. Recently, self-propagation of altered proteins that cause several neurodegenerative diseases, including Alzheimer disease and the tauopathies, has been demonstrated using cultured cell and transgenic mouse models. Increasing evidence argues that the Ab peptide acts as a prion in that it stimulates the de-novo formation of more Ab peptide. Similarly, the aggregates of Tau provoke the assembly of more aggregated Tau. In addition, fetal grafts of substantia nigra in patients with advanced Parkinson’s disease exhibit Lewy bodies, arguing that a-synuclein may act as a prion. Misfolded a-synuclein is thought to transit from the patient’s neurons to those in the graft, where it stimulates the de-novo formation of aberrantly folded a-synuclein into Lewy bodies.

    The spread of misprocessed proteins in the human CNS is also consistent with the Ab peptide, hyperphosphorylated Tau and misfolded a-synuclein being prions. In Alzheimer disease, Ab plaques and neurofibrillary tangles (NFTs) begin in the entorhinal cortex and spread throughout the brain. In a delayed form of traumatic brain injury, NFTs appear to spread outward from points of impact. Misfolded a-synuclein has been found along the vagus nerve where it appears to migrate retrograde into the CNS.

    Increasing evidence that posttranslationally altered proteins are responsible for the major neurodegenerative diseases widens the spectrum of prion disorders. Moreover, prions with glutamine/asparagine-rich regions like those in yeast and aplysia have given unique insights into the normal function of alternatively processed, self-propagating proteins.

    Oral.33: Transmission of Alzheimer Disease and Type 2 Diabetes by a Prion Mechanism

    Claudio Soto,1,† Natalia Salvadores-Bersezio,1 Ines Moreno-Gonzalez,1 Claudia Duran-Aniotz,1, 2 Akihiko Urayama,1 Lisbell Estrada,3 Diego Morales-Scheihing1, 2 and Rodrigo Morales1

    1Protein Misfolding Disorders Lab, Mitchell Center for Alzheimer Disease and Related Brain Disorders, Department of Neurology; University of Texas Medical School at Houston; Houston, TX USA; 2Facultad de Medicina, Universidad de Los Andes; Santiago, Chile; 3 Universidad Catolica de Chile; Santiago, Chile†Presenting author; Email: Claudio.Soto@uth.tmc.edu

    Alzheimer disease (AD) and type 2 diabetes (T2D) are the most prevalent diseases of the group of protein misfolding disorders (PMDs). A hallmark event in the pathology of AD and T2D involves the misfolding, aggregation and accumulation of Ab and IAPP, respectively. Considering that the molecular mechanisms responsible for protein misfolding and aggregation in PMDs are strikingly similar to the process of prion replication we hypothesize that all these diseases have the inherent capability of being transmissible. Recent exciting studies from various groups have provided strong proof-of-concept for the transmission of the pathological hallmarks of various PMDs in an experimental setting. In this presentation we will provide further evidence for the induction of AD and T2D features in animal models of these diseases upon intra-cerebral and intra-peritoneal inoculation of tissue homogenates containing Ab and IAPP aggregates, respectively. One of the key questions regarding prion-like transmissibility of other PMDs is whether this phenomenon can occur by practically relevant routes of exposure. To study this issue, we assessed whether these diseases can be induced by transfusion of blood from animals exhibiting large quantities of cerebral or pancreatic aggregates. Blood transfusion was chosen because is a medically relevant route of exposure to potentially infectious material and because the data in animals and even in humans is solid to support blood transfusion as a route of prion infection in TSEs. Our results show that infusion of blood from old AD or T2D transgenic mice into young animals significantly accelerates the onset of pathological and clinical abnormalities associated to these diseases. Our results indicate that the two most prevalent PMDs can be initiated by exposure to misfolded protein aggregates, which replicate in the body in a similar manner as infectious prions. These findings may open a new avenue to understand the origin of AD and T2D and may provide new strategies for disease intervention and prevention.

    PPPM.18: Induction of Ab Amyloidogenesis In Vivo by Blood Transfusion

    Rodrigo Morales,1,† Claudia Duran-Aniotz,1, 2 Akihiko Urayama,1 Lisbell Estrada,3 Diego Morales-Scheihing1, 2 and Claudio Soto1

    1University of Texas Health Science Center at Houston; Houston, TX USA; 2Universidad de Los Andes; Santiago, Chile; 3Universidad Catolica de Chile; Santiago, Chile†Presenting author; Email: Rodrigo.MoralesLoyola@uth.tmc.edu

    Alzheimer disease (AD) is the most common type of senile dementia. Disease manifestation is characterized by progressive impairment of memory and cognition which is triggered by synaptic dysfunction and neuronal loss. Compelling evidence suggests that misfolding and aggregation of Ab is a hallmark event in the disease pathogenesis. An important unanswered question related to AD involves its etiology since over 90% of the AD cases arise sporadically. Interestingly, misfolding and aggregation of proteins is the main feature of other diseases -termed Protein Misfolding Disorders (PMDs)] which include Transmissible Spongiform Encephalopathies (TSEs), among others. Convincing experimental evidences have shown that the only component of the infectious agent in TSEs is the misfolded form of the prion protein. Strikingly, the molecular mechanisms responsible for prion replication are very similar to the process of amyloid formation in all PMDs, suggesting that all these diseases have the inherent capability of being transmissible. Recent reports have shown that intra-cerebral and intra-peritoneal administration of brain homogenates containing Ab aggregates can accelerate the generation of senile plaques in mice models of AD. However, it remains to be demonstrated if this phenomenon can occur by more relevant routes of administration. The aim of this study was to assess whether AD pathogenesis can be induced intravenously, mimicking the know transmission of prion diseases through blood transfusion. For this purpose we used young tg2576 mice which were injected with blood obtained from 12 months old tg2576 mice (AD-blood) that contains a substantial quantity of cerebral Ab deposits. Mice were sacrificed at 250 days old, a time in which these animals scarcely develop Ab deposits. Interestingly, we observed that infusion of AD-blood induces substantial Ab accumulation in animals that without treatment or injected with wild type blood would barely have any detectable Ab lesion. Plaque deposition was mainly present in cortex and hippocampus, being more abundant in the former. In addition, we observed a decrease in memory in mice challenged with AD-blood. Other features such as brain inflammation and synaptic integrity were also measured. Importantly, similar results were obtained in a second and independent experiment performed in a double transgenic mouse model that develops AD plaques as early as 4 months old. Our results indicate that an AD-like pathogenesis can be induced by intravenous administration of AD-blood, presumably through induction of protein misfolding in a similar way as prion diseases. These findings may open a new avenue to understand the origin of sporadic AD and may provide new strategies for disease intervention and prevention.

    PPPM.20: Prion-Like Propagation and Neurotoxicity of Recombinant a-Synuclein Aggregates Initiated by Dimerization

    Alireza Roostaee† and Xavier Roucou

    University of Sherbrooke; Sherbrooke, QC Canada†Presenting author; Email: alireza.roostaee@usherbrooke.ca

    Misfolding of the a-Synuclein (a-Syn) protein and subsequent formation of amyloid fibrils or toxic aggregates are neuropathological hallmarks of Parkinson’s Disease (PD). However, a detailed characterization of the mechanism of a-synuclein aggregation/fibrillogenesis and transmission of toxic aggregates has not yet been achieved. In this study, the rates of a-Syn aggregation were compared for wild-type (wt) as well as a chimeric form of a-Syn containing an inducible Fv dimerizing domain (a-SynFv) with the capacity to form homodimers in the presence of a divalent ligand (AP20187). Here we report the increased oligomerization and fibril formation rate of recombinant a-SynFv in the presence of AP20187, in comparison to wt a-Syn or a-SynFv in the absence of divalent ligand. In addition, dimerization of a-SynFv accelerated structural transition from random coil into b-sheet conformation, which is characteristic of a-Syn aggregates. a-SynFv oligomers, but not corresponding monomers or amyloid fibrils, induced neurotoxicity when injected into the hippocampus of wt mice. These recombinant aggregates were amplified by the protein misfolding cyclic amplification (PMCA) method, providing first evidence for the in vitro propagation of synthetic a-Syn aggregates. Our results provide direct evidence for similarities between a-Syn and prion propagation and neutoxicity at the molecular level.

    http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf

    Wednesday, April 27, 2011

    GENERATION ALZHEIMER’S: THE DEFINING DISEASE OF THE BABY BOOMERS

    http://betaamyloidcjd.blogspot.com/2011/04/generation-alzheimers-defining-disease.html

    Saturday, January 22, 2011

    Alzheimer’s, Prion, and Neurological disease, and the misdiagnosis there of, a review 2011

    http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/alzheimers-prion-and-neurological.html

    Friday, September 3, 2010

    Alzheimer’s, Autism, Amyotrophic Lateral Sclerosis, Parkinson’s, Prionoids, Prionpathy, Prionopathy, TSE

    http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html

    Thursday, December 23, 2010

    Alimentary prion infections: Touch-down in the intestine, Alzheimer, Parkinson disease and TSE mad cow diseases $ The Center for Consumer Freedom

    http://betaamyloidcjd.blogspot.com/2010/12/alimentary-prion-infections-touch-down.html

    TSS

    Wednesday, July 20, 2011

    Canadian Researchers Receive $2.9 Million to Protect Against Prion Disease Outbreaks, Develop Novel Therapies to Treat Alzheimer’s, Parkinson’s and ALS

    http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/canadian-researchers-receive-29-million.html

    TSS

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