Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Polygenic risk for Alzheimer's disease shapes hippocampal scene-selectivity

Chandler, Hannah L., Hodgetts, Carl J. ORCID:, Caseras, Xavier ORCID:, Murphy, Kevin ORCID: and Lancaster, Thomas M. ORCID: 2020. Polygenic risk for Alzheimer's disease shapes hippocampal scene-selectivity. Neuropsychopharmacology 45 , pp. 1171-1178. 10.1038/s41386-019-0595-1

[thumbnail of Chambers.]
PDF - Published Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview


Preclinical models of Alzheimer’s disease (AD) suggest APOE modulates brain function in structures vulnerable to AD pathophysiology. However, genome-wide association studies now demonstrate that AD risk is shaped by a broader polygenic architecture, estimated via polygenic risk scoring (AD-PRS). Despite this breakthrough, the effect of AD-PRS on brain function in young individuals remains unknown. In a large sample (N = 608) of young, asymptomatic individuals, we measure the impact of both (i) APOE and (ii) AD-PRS on a vulnerable cortico-limbic scene-processing network heavily implicated in AD pathophysiology. Integrity of this network, which includes the hippocampus (HC), is fundamental for maintaining cognitive function during ageing. We show that AD-PRS, not APOE, selectively influences activity within the HC in response to scenes, while other perceptual nodes remained intact. This work highlights the impact of polygenic contributions to brain function beyond APOE, which could aid potential therapeutic/interventional strategies in the detection and prevention of AD.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Cardiff University Brain Research Imaging Centre (CUBRIC)
Physics and Astronomy
Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
ISSN: 0893-133X
Funders: Wellcome Trust
Date of First Compliant Deposit: 21 January 2020
Date of Acceptance: 5 December 2019
Last Modified: 05 May 2023 23:30

Citation Data

Cited 4 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics