APOE mediated neuroinflammation and neurodegeneration in Alzheimer’s disease

Elsevier

Available online 26 February 2022, 101594

Seminars in ImmunologyHighlights•

APOE4 isoform is the strongest genetic risk factor for Alzheimer’s disease.

APOE4 influences disease pathogenesis by exacerbating Aβ plaque and tau burden, associated inflammation and neurodegeneration.

Astrocytes and microglia express most APOE in the CNS.

Cell-specific APOE may promote cross-talk between microglia and astroglial subsets to perform a diverse range of functions.

Abstract

Neuroinflammation is a central mechanism involved in neurodegeneration as observed in Alzheimer’s disease (AD), the most prevalent form of neurodegenerative disease. Apolipoprotein E4 (APOE4), the strongest genetic risk factor for AD, directly influences disease onset and progression by interacting with the major pathological hallmarks of AD including amyloid-β plaques, neurofibrillary tau tangles, as well as neuroinflammation. Microglia and astrocytes, the two major immune cells in the brain, exist in an immune-vigilant state providing immunological defense as well as housekeeping functions that promote neuronal well-being. It is becoming increasingly evident that under disease conditions, these immune cells become progressively dysfunctional in regulating metabolic and immunoregulatory pathways, thereby promoting chronic inflammation-induced neurodegeneration. Here, we review and discuss how APOE and specifically APOE4 directly influences amyloid-β and tau pathology, and disrupts microglial as well as astroglial immunomodulating functions leading to chronic inflammation that contributes to neurodegeneration in AD.

Keywords

Alzheimer’s disease

Apolipoprotein E

Inflammation

Microglia

Astrocytes

Neurodegeneration

© 2022 The Authors. Published by Elsevier Ltd.

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