The Apolipoprotein E Antagonistic Pleiotropy Hypothesis: Review and Recommendations

Abstract

Research on apolipoprotein E (APOE) has consistently revealed a relationship between the gene′s ε 4 allele and risk for development of Alzheimer′s disease (AD). However, research with younger populations of ε 4 carriers has suggested that the APOE ε 4 allele may in fact be beneficial in earlier ages and may only confer risk of cognitive decline later in life. Accordingly, we and others have proposed that APOE may represent an example of antagonistic pleiotropy. Antagonistic pleiotropy is an evolutionary biology concept that proposes certain genes or alleles that may differentially impact fitness during different life stages. We critically review this hypothesis in light of new research of the impact of APOE on cognition and neural integrity across the lifespan. We provide recommendations for the revision of the antagonistic pleiotropy hypothesis of APOE and suggest important avenues for future research in this area.

Cited by papers we hold 2

• The association of APOE ε4 with cognitive function over the adult life course and incidence of dementia: 20 years follow-up of the Whitehall II study · 2021
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• Reduced Hippocampal Volume in Healthy Young ApoE4 Carriers: An MRI Study · 2012
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