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

Amy N. Murray, Hannah L. Chandler, Thomas M. Lancaster

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)33-41
Number of pages9
JournalNeurobiology of Aging
Volume98
Early online date2 Nov 2020
DOIs
Publication statusE-pub ahead of print - 2 Nov 2020

Keywords

  • Alzheimer's disease
  • Amygdala
  • Hippocampus
  • Multimodal MRI
  • Polygenic

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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