Role of Intracellular ABeta in Tau Pathology

University Of California Irvine, Irvine CA

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Abstract

DESCRIPTION (provided by applicant): Since it has been demonstrated that increasing neurofibrillary tangle (NFT) number in the Alzheimer's disease (AD) brain correlates with reduced cognitive function, elucidating the mechanisms by which tangle pathology is initiated may reveal important information regarding neuronal vulnerability in AD. The proposed studies are based upon the hypothesis that caspase-cleavage of tau at aspartate-421 is a key event in the evolution of AD NFT pathology. While our recent research efforts demonstrate that caspase-cleaved tau is very prone to filament formation in vitro and is associated with early immunohistochemical markers of AD NFT pathology, the initiating mechanisms leading to caspase proteolysis on tau are unknown. The goals of the proposed studies are to investigate the role of in vitro intracellular beta-amyloid (ABeta) as a potential initiator of the cascade leading to caspase proteolysis of tau.