Observations in APP Bitransgenic Mice Suggest that Diffuse and Compact Plaques Form via Independent Processes in Alzheimer's Disease

摘要: Studies of familial Alzheimer's disease suggest that misfolding and aggregation amyloid-β (Aβ) peptides initiate the pathogenesis. The Arctic mutation Aβ precursor protein (APP) results in AD, is more prone to form protofibrils extracellular deposits. Herein demonstrated burden diffuse deposits but not compact plaques increased when tg-Swe mice are crossed with tg-ArcSwe synthesizing low levels Aβ. bitransgenic mice, which contain primarily wild-type Aβ42, accumulate regions both without transgene expression. However, APP processing, compared tg-Swe, remains unchanged young whereas Aβ42 accelerated fibril architecture altered vitro vivo a level introduced. Thus, number likely due physical interactions between Aβ42. selective increase single type parenchymal deposit suggests different pathways lead formation plaques. These findings could have general implications for pathogenesis particular relevance patients heterozygous mutation. Moreover, it further illustrates how neuropathologic features can be manipulated by mechanisms similar those originally conceptualized prion research.