The ApoE Locus and COVID-19: Are We Going Where We Have Been?
Caleb E. Finch, Alexander M. Kulminski
Abstract
Four decades ago in 1985, alleles of apolipoprotein E (ApoE) 2/3/4 became famous for explaining 16% of genetic variance in low-density lipoprotein cholesterol in the benchmark study of Sing and Davignon (1): total blood cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B were elevated by ApoE 4 (ApoE4) allele and lowered by ApoE 2 (ApoE2). The adverse associations of ApoE4 with atherosclerosis and cardiovascular disease (CVD) (1) were extended to shortened longevity in 1987 (2) and then to risk of Alzheimer disease (AD) in 1993 (3). The next year, ApoE2 was associated with lower incidence of AD and greater longevity (4,5). ApoE is synthesized body-wide in adipocytes, hepatocytes, brain astrocytes, and arterial wall macrophages with local roles in lipid transport that are critical for brain, immune, and vascular functions.