Apolipoprotein E and Alzheimer's disease
The association of APOE with AD, the APOE isoform specific effects within brain and periphery, and potential therapeutics are reviewed.
Abstract
Genetic variation in apolipoprotein E (<i>APOE</i>) influences Alzheimer's disease (AD) risk. <i>APOE ε4</i> alleles are the strongest genetic risk factor for late onset sporadic AD. The AD risk is dose dependent, as those carrying one <i>APOE ε4</i> allele have a 2-3-fold increased risk, while those carrying two <i>ε4</i> alleles have a 10-15-fold increased risk. Individuals carrying <i>APOE ε2</i> alleles have lower AD risk and those carrying <i>APOE ε3</i> alleles have neutral risk. APOE is a lipoprotein which functions in lipid transport, metabolism, and inflammatory modulation. Isoform specific effects of APOE within the brain include alterations to A<i>β</i>, tau, neuroinflammation, and metabolism. Here we review the association of <i>APOE</i> with AD, the APOE isoform specific effects within brain and periphery, and potential therapeutics.