Apolipoprotein e metabolism and functions in brain and its role in Alzheimer's disease

Fan Liao, Hyejin Yoon, Jungsu Kim

Research output: Contribution to journalReview article

34 Scopus citations

Abstract

Purpose of review APOE4 genotype is the strongest genetic risk factor for Alzheimer's disease. Prevailing evidence suggests that amyloid βa plays a critical role in Alzheimer's disease. The objective of this article is to review the recent findings about the metabolism of apolipoprotein E (ApoE) and amyloid β and other possible mechanisms by which ApoE contributes to the pathogenesis of Alzheimer's disease. Recent findings ApoE isoforms have differential effects on amyloid b metabolism. Recent studies demonstrated that ApoE-interacting proteins, such as ATP-binding cassette A1 (ABCA1) and LDL receptor, may be promising therapeutic targets for Alzheimer's disease treatment. Activation of liver X receptor and retinoid X receptor pathway induces ABCA1 and other genes, leading to amyloid b clearance. Inhibition of the negative regulators of ABCA1, such as microRNA-33, also induces ABCA1 and decreases the levels of ApoE and amyloid β. In addition, genetic inactivation of an E3 ubiquitin ligase, myosin regulatory light chain interacting protein, increases LDL receptor levels and inhibits amyloid accumulation. Although amyloid β-dependent pathways have been extensively investigated, there have been several recent studies linking ApoE with vascular function, neuroinflammation, metabolism, synaptic plasticity, and transcriptional regulation. For example, ApoE was identified as a ligand for a microglial receptor, TREM2, and studies suggested that ApoE may affect the TREM2-mediated microglial phagocytosis. Summary Emerging data suggest that ApoE affects several amyloid b-independent pathways. These underexplored pathways may provide new insights into Alzheimer's disease pathogenesis. However, it will be important to determine to what extent each mechanism contributes to the pathogenesis of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)60-67
Number of pages8
JournalCurrent Opinion in Lipidology
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

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Keywords

  • Alzheimer's disease
  • Amyloid b
  • Apolipoprotein E
  • Lipid metabolism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Genetics
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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