APOE-e4-related differences in left thalamic microstructure in cognitively healthy adults

Mole, Jilu P., Fasano, Fabrizio, Evans, John, Sims, Rebecca ORCID: https://orcid.org/0000-0002-3885-1199, Kidd, Emma ORCID: https://orcid.org/0000-0001-5507-1170, Aggleton, John ORCID: https://orcid.org/0000-0002-5573-1308 and Metzler-Baddeley, Claudia ORCID: https://orcid.org/0000-0002-8646-1144 2020. APOE-e4-related differences in left thalamic microstructure in cognitively healthy adults. Scientific Reports 10 , 19787. 10.1038/s41598-020-75992-9

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Abstract

APOE-ε4 is a main genetic risk factor for developing late onset Alzheimer’s disease (LOAD) and is thought to interact adversely with other risk factors on the brain. However, evidence regarding the impact of APOE-ε4 on grey matter structure in asymptomatic individuals remains mixed. Much attention has been devoted to characterising APOE-ε4-related changes in the hippocampus, but LOAD pathology is known to spread through the whole of the Papez circuit including the limbic thalamus. Here, we tested the impact of APOE-ε4 and two other risk factors, a family history of dementia and obesity, on grey matter macro- and microstructure across the whole brain in 165 asymptomatic individuals (38–71 years). Microstructural properties of apparent neurite density and dispersion, free water, myelin and cell metabolism were assessed with Neurite Orientation Density and Dispersion (NODDI) and quantitative magnetization transfer (qMT) imaging. APOE-ε4 carriers relative to non-carriers had a lower macromolecular proton fraction (MPF) in the left thalamus. No risk effects were present for cortical thickness, subcortical volume, or NODDI indices. Reduced thalamic MPF may reflect inflammation-related tissue swelling and/or myelin loss in APOE-ε4. Future prospective studies should investigate the sensitivity and specificity of qMT-based MPF as a non-invasive biomarker for LOAD risk.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy Psychology
Additional Information:	Creative Commons Attribution 4.0 International License
Publisher:	Nature Publishing Group
ISSN:	2045-2322
Funders:	Wellcome Trust
Date of First Compliant Deposit:	26 October 2020
Date of Acceptance:	15 October 2020
Last Modified:	31 Aug 2023 05:22
URI:	https://orca.cardiff.ac.uk/id/eprint/135748

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