Apolipoprotein e and Alzheimer disease: Risk, mechanisms and therapy

Research output: Contribution to journalArticle

1028 Citations (Scopus)

Abstract

Apolipoprotein E (Apo-E) is a major cholesterol carrier that supports lipid transport and injury repair in the brain. APOE polymorphic alleles are the main genetic determinants of Alzheimer disease (AD) risk: individuals carrying the ε4 allele are at increased risk of AD compared with those carrying the more common ε3 allele, whereas the ε2 allele decreases risk. Presence of the APOE ε4 allele is also associated with increased risk of cerebral amyloid angiopathy and age-related cognitive decline during normal ageing. Apo-E-lipoproteins bind to several cell-surface receptors to deliver lipids, and also to hydrophobic amyloid-β (Aβ) peptide, which is thought to initiate toxic events that lead to synaptic dysfunction and neurodegeneration in AD. Apo-E isoforms differentially regulate Aβ aggregation and clearance in the brain, and have distinct functions in regulating brain lipid transport, glucose metabolism, neuronal signalling, neuroinflammation, and mitochondrial function. In this Review, we describe current knowledge on Apo-E in the CNS, with a particular emphasis on the clinical and pathological features associated with carriers of different Apo-E isoforms. We also discuss Aβ-dependent and Aβ-independent mechanisms that link Apo-E4 status with AD risk, and consider how to design effective strategies for AD therapy by targeting Apo-E.

Original languageEnglish (US)
Pages (from-to)106-118
Number of pages13
JournalNature Reviews Neurology
Volume9
Issue number2
DOIs
StatePublished - Feb 2013

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Apolipoproteins
Apolipoproteins E
Alzheimer Disease
Alleles
Lipids
Protein Isoforms
Brain
Therapeutics
Cerebral Amyloid Angiopathy
Apolipoprotein E4
Poisons
Cell Surface Receptors
Amyloid
Lipoproteins
Cholesterol
Glucose
Peptides
Wounds and Injuries

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Apolipoprotein e and Alzheimer disease : Risk, mechanisms and therapy. / Liu, Chia-Chen; Kanekiyo, Takahisa; Xu, Huaxi; Bu, Guojun D.

In: Nature Reviews Neurology, Vol. 9, No. 2, 02.2013, p. 106-118.

Research output: Contribution to journalArticle

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