Apolipoprotein E as a Therapeutic Target in Alzheimer's Disease: A Review of Basic Research and Clinical Evidence.

ABSTRACT: Alzheimer's disease (AD) is a devastating neurodegenerative disorder that causes progressive cognitive decline. The majority of AD cases are sporadic and late-onset (>65 years old) making it the leading cause of dementia in the elderly. While both genetic and environmental factors contribute to the development of late-onset AD (LOAD), APOE polymorphism is a major genetic risk determinant for LOAD. In humans, the APOE gene has three major allelic variants: ?2, ?3, and ?4, of which APOE ?4 is the strongest genetic risk factor for LOAD, whereas APOE ?2 is protective. Mounting evidence suggests that APOE ?4 contributes to AD pathogenesis through multiple pathways including facilitated amyloid-? deposition, increased tangle formation, synaptic dysfunction, exacerbated neuroinflammation, and cerebrovascular defects. Since APOE modulates multiple biological processes through its corresponding protein apolipoprotein E (apoE), APOE gene and apoE properties have been a promising target for therapy and drug development against AD. In this review, we summarize the current evidence regarding how the APOE ?4 allele contributes to the pathogenesis of AD and how relevant therapeutic approaches can be developed to target apoE-mediated pathways in AD.

SUBMITTER: Yamazaki Y 

PROVIDER: S-EPMC5526196 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature