APOE-amyloid interaction: Therapeutic targets

Neurobiol Dis. 2020 May:138:104784. doi: 10.1016/j.nbd.2020.104784. Epub 2020 Feb 4.

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that is growing in prevalence globally. It is the only major cause of death without any effective pharmacological means to treat or slow progression. Inheritance of the ε4 allele of the Apolipoprotein (APO) E gene is the strongest genetic risk factor for late-onset AD. The interaction between APOE and amyloid β (Aβ) plays a key role in AD pathogenesis. The APOE-Aβ interaction regulates Aβ aggregation and clearance and therefore directly influences the development of amyloid plaques, congophilic amyloid angiopathy and subsequent tau related pathology. Relatively few AD therapeutic approaches have directly targeted the APOE-Aβ interaction thus far. Here we review the critical role of APOE in the pathogenesis of AD and some of the most promising therapeutic approaches that focus on the APOE-Aβ interaction.

Keywords: Apolipoprotein E; Beta amyloid; Early onset AD; Immunomodulation; Interaction; Oligomers; Pathological chaperone; Peptoids; Therapy.

Publication types

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

MeSH terms

  • Alleles
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / therapy
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Apolipoprotein E4 / antagonists & inhibitors
  • Apolipoprotein E4 / metabolism
  • Apolipoproteins E / antagonists & inhibitors
  • Apolipoproteins E / metabolism*
  • Brain / metabolism
  • Drug Delivery Systems
  • Humans
  • Mice
  • Plaque, Amyloid / metabolism*

Substances

  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Apolipoproteins E