TREATMENT OF ALZHEIMER'S DISEASE WITH INHIBITORS OF APOE BINDING TO APOE RECEPTOR

摘要

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β peptide (Aβ) in the brain. Aβ is derived from amyloid precursor protein (APP) by β- and Ϝ-secretases. Apolipoprotein E receptor 2 (ApoER2) is a cell-surface receptor for apolipoprotein E. This study shows that ApoER2 interacts with Xl 1 α/β proteins and that APP forms association with ApoER2 in the presence of Xl Is. Significantly, ApoE stimulates the production of Aβ, and ApoE4 produced more Aβ than ApoE2 or ApoE3, correlating with previous studies showing that individuals with the ApoE4 polymorphism were more prone to development of AD. Thus, ApoE binding to ApoER2 on cell surface stimulates the generation of Aβ from APP. Antagonists that interfere with the ApoE-ApoER2 interaction are proposed for the treatment of AD.