Abstract 1573 Endoplasmic reticulum cholesterol turnover links Aβ function with Tau dynamics via ER-microtubule contacts in Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the pathological accumulation of amyloid-beta (Aβ) and cytoplasmic tau. Moreover, cholesterol metabolism has been implicated in AD, but how it functionally mediates Aβ and tau crosstalk is unclear. Here, we demonstrate a pivotal role for Aβ42 in driving cholesterol turnover by ACAT1 at the endoplasmic reticulum (ER) using super-resolution live cell microscopy. ER cholesterol accumulation resulted in ER spheres, novel cholesterol-rich structures that can be differentially modulated by Aβ40 versus Aβ42.