Multimodal hippocampal and amygdala subfield volumetry in polygenic risk for Alzheimer's disease

Preclinical models of Alzheimer's disease (AD) suggest that volumetric reductions in medial temporal lobe (MTL) structures manifest before clinical onset. AD polygenic risk scores (PRSs) are further linked to reduced MTL volumes (the hippocampus/amygdala); however, the relationship between PRS and specific subregions remains unclear. We determine AD-PRSs a large sample young participants (N = 730, aged 22–35 years) using multimodal (T1w/T2w) approach. first demonstrate PRSs for hippocampus/amygdala predict their respective hippocampal (pFDR < 0.05). observe negative relationships whole hippocampal/amygdala volumes. Critically, we novel associations subfields such as CA1 (? ?0.096, pFDR 0.045) fissure ?0.101, 0.041). provide evidence AD-PRS is decades This may help inform preclinical risk, providing additional specificity intervention insight into mechanisms by which common variants confer susceptibility.