Apolipoprotein E and Alzheimer's disease

Genetic variation in apolipoprotein E (APOE) influences Alzheimer's disease (AD) risk. APOE epsilon 4 alleles are the strongest genetic risk factor for late onset sporadic AD. The AD risk is dose dependent, as those carrying one APOE epsilon 4 allele have a 2-3-fold increased risk, while those carrying two epsilon 4 alleles have a 10-15-fold increased risk. Individuals carrying APOE epsilon 2 alleles have lower AD risk and those carrying APOE epsilon 3 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 beta, tau, neuroinflammation, and metabolism. Here we review the association of APOE with AD, the APOE isoform specific effects within brain and periphery, and potential therapeutics. (c) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).