The Role of Apolipoprotein E in Alzheimer's Disease

Jungsu Kim, Jacob M. Basak, David M. Holtzman

Research output: Contribution to journalReview article

852 Scopus citations

Abstract

The ε4 allele of apolipoprotein E (APOE) is the major genetic risk factor for Alzheimer's disease (AD). Although there have been numerous studies attempting to elucidate the underlying mechanism for this increased risk, how apoE4 influences AD onset and progression has yet to be proven. However, prevailing evidence suggests that the differential effects of apoE isoforms on Aβ aggregation and clearance play the major role in AD pathogenesis. Other potential mechanisms, such as the differential modulation of neurotoxicity and tau phosphorylation by apoE isoforms as well as its role in synaptic plasticity and neuroinflammation, have not been ruled out. Inconsistent results among studies have made it difficult to define whether the APOE ε4 allele represents a gain of toxic function, a loss of neuroprotective function, or both. Therapeutic strategies based on apoE propose to reduce the toxic effects of apoE4 or to restore the physiological, protective functions of apoE.

Original languageEnglish (US)
Pages (from-to)287-303
Number of pages17
JournalNeuron
Volume63
Issue number3
DOIs
StatePublished - Aug 13 2009

ASJC Scopus subject areas

  • Neuroscience(all)

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    Kim, J., Basak, J. M., & Holtzman, D. M. (2009). The Role of Apolipoprotein E in Alzheimer's Disease. Neuron, 63(3), 287-303. https://doi.org/10.1016/j.neuron.2009.06.026