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Neuroimaging and APOE Genotype: A Systematic Qualitative Review

Cherbuin N. · Leach L.S. · Christensen H. · Anstey K.J.
Centre for Mental Health Research, Australian National University, Canberra, Australia Dement Geriatr Cogn Disord 2007;24:348–362 (DOI:10.1159/000109150)


Apolipoprotein E (APOE) is the major genetic risk factor for late-onset Alzheimer’s disease (AD) and has also been implicated in cardiovascular disease, cognitive decline and cognitive changes in healthy ageing. The aim of this paper is to systematically review and critically assess the association between the APOE genotype and structural/functional cerebral changes as evidenced by brain imaging studies. A second aim is to determine whether these observed associations between APOE and the brain reflect changes which are consistent with the progression of AD neurodegenerative changes described in Braak stages. A search of Pubmed, Psycinfo, and Web of Science databases identified 64 articles available for qualitative review. The review found that presence of the APOE ε4 allele is associated with (1) hippocampal, amygdalar and entorhinal cortex atrophy, (2) increased brain atrophy, (3) increased white matter hyperintensity volumes and (4) altered cerebral blood flow and glucose metabolism patterns. It is possible that there are critical age ranges when these effects are evident and that the APOE ε2 genotype might present a risk. We conclude that structural brain change is associated with the APOE genotype and that it is more salient in younger ageing individuals.


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