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Associations between Alzheimer's disease polygenic risk scores and hippocampal subfield volumes in 17,161 UK Biobank participants

By Heidi Foo, Anbupalam Thalamuthu, Jiyang Jiang, Forrest Koch, Karen A. Mather, Wei Wen, Perminder S. Sachdev

Posted 27 Oct 2020
medRxiv DOI: 10.1101/2020.10.24.20218925

Hippocampal volume is an important biomarker of Alzheimers disease (AD), and genetic risk of AD is associated with hippocampal atrophy. However, the hippocampus is not a uniform structure and has a number of subfields, the associations of which with age, sex, and polygenic risk score for AD (PRSAD) have been inadequately investigated. We examined these associations in 17,161 cognitively normal UK Biobank participants (44-80 years). Age was negatively associated with all the hippocampal subfield volumes and females had smaller volumes than men. Higher PRSAD was associated with lower volumes in the bilateral whole hippocampus, hippocampal-amygdala-transition-area (HATA), and hippocampal tail; right subiculum; left cornu ammonis (CA)1, CA4, molecular layer, and granule cell layer of dentate gyrus (CG-DG), with associations being greater on the left side. Older individuals (median age 63 years, n=8984) showed greater subfield vulnerability to high PRSAD compared to the younger group (n=8177), but the effect did not differ by sex. The pattern of subfield involvement in relation to the PRSAD in community dwelling healthy individuals sheds additional light on the pathogenesis of AD.

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