Apolipoprotein E genotype and MRI-detected brain alterations pertaining to neurodegeneration: A systematic review

IntroductionThe effect of apolipoprotein E (APOE) genotype, particularly APOE {varepsilon}4, the main genetic risk factor for late-onset Alzheimers disease (LOAD), has been widely explored in neuroimaging studies pertaining to older adults. The goal of this systematic review was to review the literature on the relationship between carriage of the APOE {varepsilon}4 allele and grey matter (GM) changes across various age groups and its influence on neurodegeneration as evidenced by structural magnetic resonance imaging (MRI). MethodsA search of the electronic databases Pubmed, Scopus, Ovid and Cochrane was carried out till March 2020. Only studies published in English were included. Risk of bias of each study was assessed using the modified Newcastle-Ottawa Scale. ResultsA total of 115 articles met the inclusion criteria. Methodological quality varied from poor to good. There is moderate evidence of reduced GM volume in the middle frontal gyrus, precuneus, hippocampus, hippocampal subfields, amygdala, parahippocampal gyrus, middle temporal lobe, whole temporal lobe, temporal pole, and posterior cingulate cortex in APOE {varepsilon}4 carriers. ConclusionThe present data supports the utility of the hippocampal GM volume to evaluate early structural neurodegenerative changes that occurs in APOE {varepsilon}4 positive elderly individuals who are at increased risk of developing LOAD. Furthermore, the evidence supports serial measurements and comparison of hippocampal volume based on age group, to track the progression of neurodegeneration in APOE {varepsilon}4 carriers. Additional longitudinal studies are necessary to confirm whether the combination of MRI-detected hippocampal atrophy with APOE {varepsilon}4 carrier status, can better predict the development of LOAD in cognitively normal individuals.