AUTHOR=Soo Cassandra C. , Farrell Meagan T. , Tollman Stephen , Berkman Lisa , Nebel Almut , Ramsay Michèle 

TITLE=Apolipoprotein E Genetic Variation and Its Association With Cognitive Function in Rural-Dwelling Older South Africans

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.689756

DOI=10.3389/fgene.2021.689756

ISSN=1664-8021

ABSTRACT=<p>Apolipoprotein E (<italic>APOE</italic>) 𝜀4 allele carrier status is well known for its association with an increased likelihood of developing Alzheimer’s disease, but its independent role in cognitive function is unclear. <italic>APOE</italic> genetic variation is understudied in African populations; hence, this cross-sectional study in a rural South African community examined allele and genotype frequencies, and their associations with cognitive function. Cognitive function was assessed using two different screening methods to produce a total cognition score and four domain-specific cognition scores for verbal episodic memory, executive function, language, and visuospatial ability. Cognitive phenotype and <italic>APOE</italic> genotype data were used to determine whether <italic>APOE</italic> variation was significantly associated with cognitive function in this population. Observed allele frequencies for 1776 participants from the HAALSI study [age 40–80years (mean=56.19); 58.2% female] were 58.1% (𝜀3), 25.4% (𝜀4) and 16.5% (𝜀2). Allele distributions were similar to the African super population, but different from all non-African super populations from the 1,000 Genomes Project. The 𝜀3 homozygous genotype was most common (34.9%) and used as the base genotype for comparison in regression models. Four models were tested for each of the five cognitive phenotypes to explore association of <italic>APOE</italic> variation with cognitive function. In the first model assessing association with all genotypes for all individuals, marginally significant associations were observed for 𝜀2 homozygotes where executive function scored higher by ~0.5 standard deviations (<italic>p</italic>=0.037, SE=0.23), and for 𝜀3/𝜀4 heterozygotes where visuospatial ability scores were lower (<italic>p</italic>=0.046, SE=0.14). These did not survive correction for multiple testing. Regional African population differences were observed at the <italic>APOE</italic> locus. Marginally, significant associations between <italic>APOE</italic> genotype, and executive function and visuospatial ability indicate the need for larger studies to better examine these associations in African populations. Furthermore, longitudinal data could shed light on <italic>APOE</italic> genetic association with rate of change, or decline, in cognitive function.</p>