Linking amyloid and tau pathology in Alzheimer's disease: the role of membrane cholesterol in Abeta-mediated tau toxicity.

摘要

Alzheimer's disease (AD) is characterized by extracellular deposition of beta-amyloid (Abeta) as senile plaques, as well as intracel-lular accumulation of hyperphosphory-lated, aggregated tau as neurofibrillary tangles. Increased production and/or deposition of Abeta is thought to precede tangle formation, but evidence suggests that tau pathology is more closely related to neuronal death (reviewed by Hanger et al, 2009). The importance of tau in mediating Abeta toxicity has been demonstrated by the resistance of tau knock-out neurons to Abetainduced neurotoxicity and the rescue of cognitive impairment in mutant amyloid precursor protein (APP) trans-genic mice when crossed with a tau knock-out line (Roberson et al., 2007).