Apolipoprotein E: Structural Insights and Links to Alzheimer Disease Pathogenesis

Neuron. 2021 Jan 20;109(2):205-221. doi: 10.1016/j.neuron.2020.10.008. Epub 2020 Nov 10.

Abstract

Apolipoprotein E (ApoE) is of great interest due to its role as a cholesterol/lipid transporter in the central nervous system (CNS) and as the most influential genetic risk factor for Alzheimer disease (AD). Work over the last four decades has given us important insights into the structure of ApoE and how this might impact the neuropathology and pathogenesis of AD. In this review, we highlight the history and progress in the structural and molecular understanding of ApoE and discuss how these studies on ApoE have illuminated the physiology of ApoE, receptor binding, and interaction with amyloid-β (Aβ). We also identify future areas of study needed to advance our understanding of how ApoE influences neurodegeneration.

Keywords: AD; Alzheimer disease; Amyloid-β; ApoE; Apolipoprotein E; Aβ; LDLR; low-density lipoprotein receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Animals
  • Apolipoproteins E / chemistry*
  • Apolipoproteins E / metabolism*
  • Brain / metabolism
  • Brain / pathology
  • Humans
  • Protein Multimerization / physiology
  • Protein Structure, Secondary
  • Protein Transport / physiology
  • Receptors, LDL / chemistry
  • Receptors, LDL / metabolism

Substances

  • Apolipoproteins E
  • LDLR protein, human
  • Receptors, LDL