Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol

The accumulation of amyloid β (Aβ) in the brain appears to be a necessary event in the pathogenesis of Alzheimer's disease (AD). However, processes linked to the endogenous regulation of Aβ production are still not completely understood. Here, the authors show that Aβ accumulation in neurons is tightly regulated by cholesterol synthesis and apoE transport from astrocytes. The study provides a molecular context for understanding the endogenous regulation of Aβ accumulation and why it correlates with AD. The tight regulation suggests that Aβ may perform an important cellular function. A complete understanding of the mechanism is likely necessary to predict whether the selective removal of Aβ has potential for a therapeutic benefit.