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However, evidence regarding the impact of<jats:italic>APOE<\/jats:italic>-\u03b54 on grey matter structure in asymptomatic individuals remains mixed. Much attention has been devoted to characterising<jats:italic>APOE<\/jats:italic>-\u03b54-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<jats:italic>APOE<\/jats:italic>-\u03b54 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\u201371\u00a0years). 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.<jats:italic>APOE<\/jats:italic>-\u03b54 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<jats:italic>APOE<\/jats:italic>-\u03b54. Future prospective studies should investigate the sensitivity and specificity of qMT-based MPF as a non-invasive biomarker for LOAD risk.<\/jats:p>","DOI":"10.1038\/s41598-020-75992-9","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T11:02:55Z","timestamp":1605265375000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["APOE-\u03b54-related differences in left thalamic microstructure in cognitively healthy adults"],"prefix":"10.1038","volume":"10","author":[{"given":"Jilu P.","family":"Mole","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Fasano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Sims","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Kidd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Aggleton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Metzler-Baddeley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,13]]},"reference":[{"key":"75992_CR1","unstructured":"World Health Organisation. 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