Apolipoprotein E and Amyloid-β-Independent Mechanisms in Alzheimer's Disease

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Apolipoprotein E (apoE) is a key protein linked to the pathogenesis of Alzheimer's disease (AD) beyond its central roles in lipid metabolism. Among the three human APOE gene alleles, APOE4 is the strongest genetic risk factor for AD, while APOE2 is protective. Although apoE isoforms regulate amyloid-β (Aβ) metabolism with apoE4 exacerbating Aβ deposition, emerging evidence indicates that apoE isoforms influence cognition through various pathways in Aβ-independent manners. ApoE isoforms also regulate neuronal cholesterol metabolism, brain glucose metabolism, mitochondrial functions, cerebrovascular system, and immune responses, which substantially contribute to AD pathogenesis. Therefore, apoE isoforms likely regulate critical pathways influencing brain homeostasis and cognition independent of Aβ-related effects. Better understanding of the link between apoE isoforms and Aβ-independent mechanisms in AD pathogenesis should allow us to define novel targets for AD therapy.

Original languageEnglish (US)
Title of host publicationGenes, Environment and Alzheimer's Disease
PublisherElsevier Inc.
Pages171-196
Number of pages26
ISBN (Print)9780128028513
DOIs
StatePublished - 2016

Fingerprint

Apolipoproteins E
Amyloid
Alzheimer Disease
Protein Isoforms
Cognition
Apolipoproteins A
Apolipoprotein E4
Critical Pathways
Brain
Lipid Metabolism
Immune System
Homeostasis
Alleles
Cholesterol
Glucose
Genes
Proteins

Keywords

  • Alzheimer's disease
  • ApoE
  • Cerebrovascular system
  • Cholesterol metabolism
  • Cognitive decline
  • Glucose metabolism
  • Insulin signaling
  • Mitochondria functions
  • Neuroinflammation

ASJC Scopus subject areas

  • Medicine(all)
  • Neuroscience(all)

Cite this

Apolipoprotein E and Amyloid-β-Independent Mechanisms in Alzheimer's Disease. / Kanekiyo, Takahisa; Bu, Guojun D.

Genes, Environment and Alzheimer's Disease. Elsevier Inc., 2016. p. 171-196.

Research output: Chapter in Book/Report/Conference proceedingChapter

Kanekiyo, Takahisa ; Bu, Guojun D. / Apolipoprotein E and Amyloid-β-Independent Mechanisms in Alzheimer's Disease. Genes, Environment and Alzheimer's Disease. Elsevier Inc., 2016. pp. 171-196
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