Dr. Jekyll and Mr. Hyde: ApoE explains opposing effects of neuronal LRP1

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia, and its pathogenesis is initiated by the accumulation of amyloid-&bgr; (A&bgr;) into extracellular plaques. Apolipoprotein E4 (ApoE4) is the largest genetic risk factor for sporadic AD and contributes to AD pathogenesis by influencing clearance and seeding of the initial aggregation of A&bgr;. In this issue of the JCI, Tachibana et al. investigated the relationship between neuronal LRP1 expression and ApoE4-mediated seeding of A&bgr; and showed that knockout of neuronal LRP1 prevents the increase in A&bgr; pathology caused by ApoE4 expression. These findings give insight into potential therapeutic targets for the preclinical phase of AD and the pathogenesis of A&bgr; pathology.