Molecular Insight into the Therapeutic Promise of TargetingAPOE4for Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that causes chronic cognitive dysfunction. Most of the AD cases are late onset, and the apolipoprotein E (APOE) isoform is a key genetic risk factor. TheAPOEgene has 3 key alleles in humans includingAPOE2,APOE3, andAPOE4. Among them,APOE4is the most potent genetic risk factor for late-onset AD (LOAD), whileAPOE2has a defensive effect. Research data suggest thatAPOE4leads to the pathogenesis of AD through various processes such as accelerated beta-amyloid aggregations that raised neurofibrillary tangle formation, cerebrovascular diseases, aggravated neuroinflammation, and synaptic loss. However, the precise mode of actions regarding in what wayAPOE4leads to AD pathology remains unclear. SinceAPOEcontributes to several pathological pathways of AD, targetingAPOE4might serve as a promising strategy for the development of novel drugs to combat AD. In this review, we focus on the recent studies aboutAPOE4-targeted therapeutic strategies that have been advanced in animal models and are being prepared for use in humans for the management of AD.