Membrane cholesterol modulates {beta}-amyloid-dependent tau cleavage by inducing changes in the membrane content and localization of N-methyl-D-aspartic acid receptors.

ABSTRACT: We have previously shown that β-amyloid (Aβ) treatment resulted in an age-dependent calpain activation leading to Tau cleavage into a neurotoxic 17-kDa fragment in a cellular model of Alzheimer disease. This detrimental cellular response was mediated by a developmentally regulated increase in membrane cholesterol levels. In this study, we assessed the molecular mechanisms by which cholesterol modulated Aβ-induced Tau cleavage in cultured hippocampal neurons. Our results indicated that these mechanisms did not involve the regulation of the binding of Aβ aggregates to the plasma membrane. On the other hand, experiments using N-methyl-d-aspartic acid receptor inhibitors suggested that these receptors played an essential role in cholesterol-mediated Aβ-dependent calpain activity and 17-kDa Tau

SUBMITTER: Nicholson AM 

PROVIDER: S-EPMC3020782 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature