PerspectiveRevision of the apolipoprotein E compensatory mechanism recruitment hypothesis

The association between the apolipoprotein E ε4 allele and Alzheimer's disease (AD) is well-established. Functional neuroimaging research has supported a compensatory mechanism recruitment hypothesis whereby nondemented ε4 participants use additional cognitive resources to buffer against episodic memory declines in older age, a mechanism that is presumably associated with encroaching disease. However, recent studies have implicated a beneficial effect associated with the ε4 allele early in the life span. These studies suggest a revised hypothesis whereby ε4 persons perform better on cognitive measures early in the life span and then show greater recruitment of brain regions during performance to compensate for declines in older age caused by preclinical AD.