Apolipoprotein E: Implications for AD neurobiology, epidemiology and risk assessment

Alzheimer disease (AD) is a common and devastating dementing illness for which there is no effective neuroprotective therapy or cure. The presence of the apolipoprotein E (apoE) ε4 allele is a well-established genetic modifier (risk factor) of sporadic AD. In this review, we provide an update on the implications of apoE for the neurobiology and epidemiology of AD. Moreover, recent evidence is adduced indicating that (i) many AD risk factors are potentially modifiable by adaptive lifestyle changes and pharmacotherapy and (ii) the potency of these modifiable AD determinants and responsiveness to intervention are often significantly impacted by the presence or absence of the ε4 allele. Delineation of the influences of the APOE genotype on modifiable AD risk factors and prevention may spur consideration of APOE testing for presymptomatic individuals seeking to define their personal risk.