Apolipoprotein E, Receptors, and Modulation of Alzheimer's Disease

Na Zhao, Chia Chen Liu, Wenhui Qiao, Guojun Bu

Research output: Contribution to journalReview articlepeer-review

109 Scopus citations

Abstract

Apolipoprotein E (apoE) is a lipid carrier in both the peripheral and the central nervous systems. Lipid-loaded apoE lipoprotein particles bind to several cell surface receptors to support membrane homeostasis and injury repair in the brain. Considering prevalence and relative risk magnitude, the ε4 allele of the APOE gene is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). ApoE4 contributes to AD pathogenesis by modulating multiple pathways, including but not limited to the metabolism, aggregation, and toxicity of amyloid-β peptide, tauopathy, synaptic plasticity, lipid transport, glucose metabolism, mitochondrial function, vascular integrity, and neuroinflammation. Emerging knowledge on apoE-related pathways in the pathophysiology of AD presents new opportunities for AD therapy. We describe the biochemical and biological features of apoE and apoE receptors in the central nervous system. We also discuss the evidence and mechanisms addressing differential effects of apoE isoforms and the role of apoE receptors in AD pathogenesis, with a particular emphasis on the clinical and preclinical studies related to amyloid-β pathology. Finally, we summarize the current strategies of AD therapy targeting apoE, and postulate that effective strategies require an apoE isoform–specific approach.

Original languageEnglish (US)
Pages (from-to)347-357
Number of pages11
JournalBiological psychiatry
Volume83
Issue number4
DOIs
StatePublished - Feb 15 2018

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Apolipoprotein E
  • Low-density lipoprotein receptor family
  • Synaptic plasticity
  • Tauopathy

ASJC Scopus subject areas

  • Biological Psychiatry

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