Caveolae, CD109, and endothelial cells as targets for treating Alzheimer's disease

Abstract

Reduced functionality of transforming growth factor β (TGF-β) is a major pathogenetic component of Alzheimer's disease (AD). The reduction is caused by an ≈50% decrease in the AD brain of the TGF-β receptor, TGFBR, causing a bottleneck effect that reduces the downstream actions of TGF-β, which is highly disadvantageous for brain function. Degradation of TGFBR occurs in caveolae with participation by caveolin-1 (Cav-1) and CD109. Mechanisms for this are discussed. In the cerebral microcirculation, endothelial cells (which are rich in caveolae) carry CD109 as a surface marker that co-precipitates with Cav-1. Atorvastatin reduced Cav-1 by 75% and, because Cav-1 and CD109 co-immunoprecipitate reciprocally, atorvastatin would also reduce the level of CD109. Administration of atorvastatin as a component of combination therapy would diminish the degradation of TGFBR and thereby benefit patients with AD.