Title:APOE4 is a Risk Factor and Potential Therapeutic Target for Alzheimer's Disease
Volume: 23
Issue: 3
Author(s): Gunel Ayyubova*
Affiliation:
- Department of Cytology, Embryology and Histology, Azerbaijan Medical University, Baku, Azerbaijan
Keywords:
Apolipoprotein E, amyloid β, Alzheimer’s disease, microglia, tau, lipid metabolism, CNS.
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease, the main pathological
hallmark of which is the loss of neurons, resulting in cognitive and memory impairments. Sporadic
late-onset AD is a prevalent form of the disease and the apolipoprotein E4 (APOE4) genotype is the
strongest predictor of the disease development. The structural variations of APOE isoforms affect their
roles in synaptic maintenance, lipid trafficking, energy metabolism, inflammatory response, and BBB
integrity. In the context of AD, APOE isoforms variously control the key pathological elements of
the disease, including Aβ plaque formation, tau aggregation, and neuroinflammation. Taking into
consideration the limited number of therapy choices that can alleviate symptoms and have little impact
on the AD etiology and progression to date, the precise research strategies guided by apolipoprotein E
(APOE) polymorphisms are required to assess the potential risk of age-related cognitive decline
in people carrying APOE4 genotype. In this review, we summarize the evidence implicating the
significance of APOE isoforms on brain functions in health and pathology with the aim to identify the
possible targets that should be addressed to prevent AD manifestation in individuals with the APOE4
genotype and to explore proper treatment strategies.
