Premium
S4–01–01: Seeded initiation and spread of aggregated beta‐amyloid
Author(s) -
Walker Lary
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.04.316
Subject(s) - amyloid (mycology) , cerebral amyloid angiopathy , neocortex , biochemistry of alzheimer's disease , amyloid beta , beta (programming language) , genetically modified mouse , chemistry , biophysics , bace1 as , extracellular , amyloid precursor protein , p3 peptide , neuroscience , biology , pathology , microbiology and biotechnology , transgene , biochemistry , alzheimer's disease , medicine , disease , peptide , dementia , gene , computer science , programming language
Background: The deposition of beta-amyloid is inducible in the brains of susceptible hosts by seeds consisting of aggregated beta-amyloid. Current evidence favors the view that the corruptive templating of beta-amyloid is similar to the process by which prions convey their pathogenic structural features to na€ıve prion protein molecules. In Alzheimer’s disease, the proteinaceous lesions appear to arise endogenously and then spread systematically to other brain areas. beta-amyloid seeds thus are a potential vector for the amplification of proteinaceous aggregates in vivo. The cellular mechanisms by which beta-amyloid seeds travel from one place to another remain poorly understood. Methods: Using an established exogenous seeding paradigm, beta-amyloid-rich brain extracts were infused into the hippocampal formation or neocortex of APP-transgenic rodents. The temporal and spatial disposition of the seeds and of the subsequently induced deposits were analyzed. Results: The local pattern of exogenously seeded beta-amyloid deposition is governed to a considerable extent by simple diffusion of the injected brain extract. When beta-amyloid deposition is focally induced by beta-amyloid seeds in one brain region, other areas are subsequently beset by beta-amyloid aggregates. The secondarily affected areas contain extracellular deposits (which generally emerge systematically in axonally interconnected regions) and/or vascular deposits (cerebral amyloid angiopathy). Conclusions: Beta-amyloid deposition can be seeded in the brains of transgenic rodents by beta-amyloid-rich brain extracts. Once the seeding of beta-amyloid has been initiated, cellular (and possibly vascular) mechanisms promote the continued ramification of beta-amyloid aggregation at distal sites. Key Collaborators: Amarallys Cintron, Rebecca Rosen, Harry LeVine III, and Mathias Jucker and colleagues in T€ubingen, Germany.