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-beta peptide (Abeta) in the brain. Abeta is derived from amyloid precursor protein (APP) by beta- and gamma-secretases. Apolipoprotein E receptor 2 (ApoER2) is a cell-surface receptor for apolipoprotein E. This study shows that ApoER2 interacts with X11alpha/beta proteins and that APP forms association with ApoER2 in the presence of X11s. Significantly, ApoE stimulates the production of Abeta, and ApoE4 produced more Abeta 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 Abeta from APP. Antagonists that interfere with the ApoE-ApoER2 interaction are proposed for the treatment of AD.