Revision of the apolipoprotein E compensatory mechanism recruitment hypothesis

The association between the apolipoprotein E epsilon 4 allele and Alzheimer's disease (AD) is well-established. Functional neuroimaging research has supported a compensatory mechanism recruitment hypothesis whereby nondemented epsilon 4 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 epsilon 4 allele early in the life span. These studies suggest a revised hypothesis whereby epsilon 4 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. (C) 2008 The Alzheimer's Association. All rights reserved.