Alzheimer's Disease Therapeutics Targeting Apolipoprotein E

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The apolipoprotein E (APOE) gene strongly affects risk for Alzheimer's disease (AD). The ε4 allele increases whereas the ε2 allele decreases risk relative to the ε3 allele. The apoE protein is produced predominantly by astrocytes in the brain, and a large body of literature indicates that apoE plays a role in AD pathogenesis mainly by affecting amyloid-β (Aβ) aggregation and clearance, which influences the onset, amount, and location of Aβ deposition into either amyloid plaques or cerebral amyloid angiopathy. ApoE may also modify AD pathogenesis by additional Aβ-independent mechanisms. ApoE genotype, levels, and lipidation status influence apoE function and its likely role in AD pathogenesis. Since the exact mechanism by which apoE affects AD pathogenesis is not entirely clear, apoE targeting therapeutics are still at an early stage. Current proposed strategies include blocking the apoE/Aβ interaction, apoE passive immunotherapy, and modifying apoE levels, structure, lipidation, or fragmentation.

Original languageEnglish
Title of host publicationDeveloping Therapeutics for Alzheimer's Disease
Subtitle of host publicationProgress and Challenges
PublisherElsevier Inc.
Pages271-303
Number of pages33
ISBN (Electronic)9780128021644
ISBN (Print)9780128021736
DOIs
StatePublished - Jun 15 2016

Keywords

  • ATP-binding cassette transporter
  • Alzheimer's disease
  • Amyloid β
  • Apolipoprotein E
  • Cerebral amyloid angiopathy
  • Low-density lipoprotein receptor

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  • Cite this

    Liao, F., & Holtzman, D. M. (2016). Alzheimer's Disease Therapeutics Targeting Apolipoprotein E. In Developing Therapeutics for Alzheimer's Disease: Progress and Challenges (pp. 271-303). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-802173-6.00010-1