Perspectives on the Role of APOE4 as a Therapeutic Target for Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease that is coupled with chronic cognitive dysfunction. AD cases are mostly late onset, and genetic risk factors like the Apolipoprotein E (APOE) play a key role in this process. APOE ɛ2, APOE ɛ3, and APOE ɛ4 are three key alleles in the human APOE gene. For late onset, APOE ɛ4 has the most potent risk factor while APOE ɛ2 plays a defensive role. Several studies suggests that APOE ɛ4 causes AD via different processes like neurofibrillary tangle formation by amyloid-β accumulation, exacerbated neuroinflammation, cerebrovascular disease, and synaptic loss. But the pathway is still unclear that which actions of APOE ɛ4 lead to AD development. Since APOE was found to contribute to many AD pathways, targeting APOE ɛ4 can lead to a hopeful plan of action in development of new drugs to target AD. In this review, we focus on recent studies and perspectives, focusing on APOE ɛ4 as a key molecule in therapeutic strategies.