Document Detail


Purified and synthetic Alzheimer's amyloid beta (Aβ) prions.
MedLine Citation:
PMID:  22711819     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aggregation and deposition of amyloid-β (Aβ) peptides are believed to be central events in the pathogenesis of Alzheimer's disease (AD). Inoculation of brain homogenates containing Aβ aggregates into susceptible transgenic mice accelerated Aβ deposition, suggesting that Aβ aggregates are capable of self-propagation and hence might be prions. Recently, we demonstrated that Aβ deposition can be monitored in live mice using bioluminescence imaging (BLI). Here, we use BLI to probe the ability of Aβ aggregates to self-propagate following inoculation into bigenic mice. We report compelling evidence that Aβ aggregates are prions by demonstrating widespread cerebral β-amyloidosis induced by inoculation of either purified Aβ aggregates derived from brain or aggregates composed of synthetic Aβ. Although synthetic Aβ aggregates were sufficient to induce Aβ deposition in vivo, they exhibited lower specific biological activity compared with brain-derived Aβ aggregates. Our results create an experimental paradigm that should lead to identification of self-propagating Aβ conformations, which could represent novel targets for interrupting the spread of Aβ deposition in AD patients.
Authors:
Jan Stöhr; Joel C Watts; Zachary L Mensinger; Abby Oehler; Sunny K Grillo; Stephen J DeArmond; Stanley B Prusiner; Kurt Giles
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-18
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-04     Completed Date:  2012-09-18     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11025-30     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aging / metabolism
Alzheimer Disease / metabolism*
Amyloid beta-Peptides / chemical synthesis*,  genetics,  isolation & purification,  metabolism*
Amyloidosis / metabolism*
Animals
Brain / metabolism
Disease Models, Animal
Female
Glial Fibrillary Acidic Protein / metabolism
Humans
Luciferases / genetics
Male
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Transgenic
Nerve Degeneration / metabolism
Prions / chemical synthesis*,  genetics,  isolation & purification,  metabolism*
Grant Support
ID/Acronym/Agency:
AG02132/AG/NIA NIH HHS; AG021601/AG/NIA NIH HHS; AG031220/AG/NIA NIH HHS; AG10770/AG/NIA NIH HHS; NS041997/NS/NINDS NIH HHS; P01 AG010770/AG/NIA NIH HHS; R37 AG031220/AG/NIA NIH HHS; //Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Glial Fibrillary Acidic Protein; 0/Prions; EC 1.13.12.-/Luciferases
Comments/Corrections

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