Molecular Insight into the Therapeutic Promise of Targeting<i>APOE4</i>for Alzheimer’s Disease

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. The APOE gene has 3 key alleles in humans including APOE2 , APOE3 , and APOE4 . Among them, APOE4 is the most potent genetic risk factor for late-onset AD (LOAD), while APOE2 has a defensive effect. Research data suggest that APOE4 leads 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 way APOE4 leads to AD pathology remains unclear.…