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

Murray, Amy N., Chandler, Hannah L. and Lancaster, Thomas M. ORCID: https://orcid.org/0000-0003-1322-2449 2021. Multimodal hippocampal and amygdala subfield volumetry in polygenic risk for Alzheimer's disease. Neurobiology of Aging 98 , pp. 33-41. 10.1016/j.neurobiolaging.2020.08.022

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Abstract

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

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Cardiff University Brain Research Imaging Centre (CUBRIC)
Additional Information:	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Publisher:	Elsevier
ISSN:	0197-4580
Funders:	Wellcome Trust
Date of First Compliant Deposit:	11 December 2020
Date of Acceptance:	2 August 2020
Last Modified:	05 May 2023 06:27
URI:	https://orca.cardiff.ac.uk/id/eprint/136927

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