ApoE: The Non-Protagonist Actor in Neurological Diseases

Genes (Basel). 2024 Oct 30;15(11):1397. doi: 10.3390/genes15111397.

Abstract

Background: Apolipoprotein E (APOE = gene, ApoE = protein) is a glycoprotein involved in the biological process of lipid transportation and metabolism, contributing to lipid homeostasis. APOE has been extensively studied for its correlation with neurodegenerative diseases, in particular Alzheimer's disease (AD), where the possession of the epsilon 4 (E4) allele is established as a risk factor for developing AD in non-familiar sporadic forms. Recently, evidence suggests a broad involvement of E4 also in other neurological conditions, where it has been shown to be a predictive marker for worse clinical outcomes in Parkinson's disease (PD), brain trauma, and disturbances of consciousness. The mechanisms underlying these associations are complex and involve amyloid-β (Aβ) peptide accumulation and neuroinflammation, although many others have yet to be identified.

Objectives: The aim of this review is to overview the current knowledge on ApoE as a non-protagonist actor in processes underlying neurodegenerative diseases and its clinical significance in AD, PD, acquired brain trauma, and Disorders of Consciousness (DoC). Ethical implications of genetic testing for APOE variants and information disclosure will also be briefly discussed.

Keywords: Alzheimer’s disease; Parkinson’s disease; apolipoprotein E; brain injury; dementia; neurodegenerative diseases; neuroinflammation; stroke.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Apolipoprotein E4 / genetics
  • Apolipoproteins E* / genetics
  • Consciousness Disorders / genetics
  • Consciousness Disorders / metabolism
  • Humans
  • Nervous System Diseases / genetics
  • Neurodegenerative Diseases / genetics
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism

Substances

  • Apolipoproteins E
  • ApoE protein, human
  • Amyloid beta-Peptides
  • Apolipoprotein E4

Grants and funding

This research received no external funding.