Current insights into apolipoprotein E and the immune response in Alzheimer's disease

Immunol Rev. 2024 Oct;327(1):43-52. doi: 10.1111/imr.13414. Epub 2024 Oct 24.

Abstract

Alzheimer's disease (AD) is a progressive neurological disorder and the most common cause of dementia. Genetic analyses identified apolipoprotein E (APOE) as the strongest genetic risk for late-onset AD. Studies have shown that ApoE modulates AD pathogenesis in part by influencing amyloid-β (Aβ) deposition. However, ApoE also appears to regulate elements of AD via regulation of innate immune response, especially through microglial and astrocyte activation. In model systems, it also regulates changes in T-cells. This review focuses on the key findings that have advanced our understanding of the role of ApoE in the pathogenesis of AD and the current view of innate immune response regulated by ApoE in AD, while discussing open questions and areas for future research.

Keywords: Alzheimer's disease; apolipoprotein E; immune responses.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / etiology
  • Alzheimer Disease* / immunology
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides* / immunology
  • Amyloid beta-Peptides* / metabolism
  • Animals
  • Apolipoproteins E* / genetics
  • Apolipoproteins E* / metabolism
  • Astrocytes / immunology
  • Astrocytes / metabolism
  • Genetic Predisposition to Disease
  • Humans
  • Immunity, Innate*
  • Microglia* / immunology
  • Microglia* / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Apolipoproteins E
  • Amyloid beta-Peptides