{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T11:30:43Z","timestamp":1772796643030,"version":"3.50.1"},"reference-count":67,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T00:00:00Z","timestamp":1725321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Ministry of Education\u2019s Humanity and Social Sciences Project","award":["23YJA190001"],"award-info":[{"award-number":["23YJA190001"]}]},{"name":"China Ministry of Education\u2019s Humanity and Social Sciences Project","award":["ARUK-SRF2017B-1"],"award-info":[{"award-number":["ARUK-SRF2017B-1"]}]},{"name":"China Ministry of Education\u2019s Humanity and Social Sciences Project","award":["NIHR203321"],"award-info":[{"award-number":["NIHR203321"]}]},{"name":"Alzheimer\u2019s Research UK Senior Research Fellowship","award":["23YJA190001"],"award-info":[{"award-number":["23YJA190001"]}]},{"name":"Alzheimer\u2019s Research UK Senior Research Fellowship","award":["ARUK-SRF2017B-1"],"award-info":[{"award-number":["ARUK-SRF2017B-1"]}]},{"name":"Alzheimer\u2019s Research UK Senior Research Fellowship","award":["NIHR203321"],"award-info":[{"award-number":["NIHR203321"]}]},{"name":"National Institute for Health and Care Research (NIHR) Sheffield Biomedical Research Centre","award":["23YJA190001"],"award-info":[{"award-number":["23YJA190001"]}]},{"name":"National Institute for Health and Care Research (NIHR) Sheffield Biomedical Research Centre","award":["ARUK-SRF2017B-1"],"award-info":[{"award-number":["ARUK-SRF2017B-1"]}]},{"name":"National Institute for Health and Care Research (NIHR) Sheffield Biomedical Research Centre","award":["NIHR203321"],"award-info":[{"award-number":["NIHR203321"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: The pathophysiology of Alzheimer\u2019s disease (AD) may begin developing years or even decades prior to the manifestation of its first symptoms. The APOE \u03b54 genotype is a prominent genetic risk for AD that has been found to be associated with brain changes across the lifespan since early adulthood. Thus, studying brain changes that may occur in young adults with an APOE \u03b54 status is highly relevant. Objective: Examine potential differences in grey matter (GM) and functional connectivity (FC) in brains of cognitively healthy young APOE \u03b54 carriers and non-carriers, denoted here as \u03b54(+) and \u03b54(\u2212), respectively. Methods: Three Tesla magnetic resonance imaging (MRI) brain scans were acquired from cognitively healthy young participants aged approximately 20 years (n = 151). Voxel-based morphometry (VBM) analysis was employed to identify potential structural differences in GM between \u03b54(+) and \u03b54(\u2212). In a subsequent seed-based connectivity (SBC) analysis, brain regions that structurally differed in the VBM analysis were considered as seeds and correlated with all the remaining voxels across the brains to then measure the differences in FC between groups. Results: The VBM analysis suggested that \u03b54(+) (n = 28) had greater GM densities relative to \u03b54(\u2212) (n = 123) in the left hippocampus and the left posterior insula (puncorr &lt; 0.001). However, the effect did not survive the correction for multiple comparisons, suggesting minimal structural differences in this age range. In contrast, the SBC analysis indicated that \u03b54(+) exhibited significantly decreased FC between the left hippocampus and areas of the left middle temporal gyrus (n = 27) compared to \u03b54(\u2212) (n = 102). These results remained significant after multiple comparisons (pFDR &lt; 0.05). Lastly, no statistically significant differences in FC between groups were observed for the left insular seed (pFDR &gt; 0.05). Discussion: These results suggest early structural and functional brain changes associated with the APOE \u03b54 genotype on young adults. Yet, they must be cautiously interpreted and contrasted with both older adults with genetic risk for AD and patients diagnosed with AD.<\/jats:p>","DOI":"10.3390\/jcm13175228","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T12:22:33Z","timestamp":1725366153000},"page":"5228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Differences in Grey Matter Concentrations and Functional Connectivity between Young Carriers and Non-Carriers of the APOE \u03b54 Genotype"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4160-7875","authenticated-orcid":false,"given":"Carlos","family":"Mu\u00f1oz-Neira","sequence":"first","affiliation":[{"name":"Artificial Intelligence & Computational Neuroscience Group (AICN Group), Sheffield Institute for Translational Neuroscience (SITraN), Division of Neuroscience, School of Medicine and Population Health, Faculty of Health, University of Sheffield, Sheffield S10 2HQ, UK"},{"name":"Old Age Psychiatry Research Group (OAP Group), Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0440-6684","authenticated-orcid":false,"given":"Jianmin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Sino-Britain Centre for Cognition and Ageing Research, Faculty of Psychology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0769-9542","authenticated-orcid":false,"given":"Ludmila","family":"Kucikova","sequence":"additional","affiliation":[{"name":"Artificial Intelligence & Computational Neuroscience Group (AICN Group), Sheffield Institute for Translational Neuroscience (SITraN), Division of Neuroscience, School of Medicine and Population Health, Faculty of Health, University of Sheffield, Sheffield S10 2HQ, UK"},{"name":"Insigneo Institute for In Silico Medicine, University of Sheffield, Sheffield S1 3JD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-1188","authenticated-orcid":false,"given":"Weijie","family":"Huang","sequence":"additional","affiliation":[{"name":"Artificial Intelligence & Computational Neuroscience Group (AICN Group), Sheffield Institute for Translational Neuroscience (SITraN), Division of Neuroscience, School of Medicine and Population Health, Faculty of Health, University of Sheffield, Sheffield S10 2HQ, UK"},{"name":"Old Age Psychiatry Research Group (OAP Group), Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SZ, UK"},{"name":"School of Systems Science, Beijing Normal University, Beijing 100875, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiong","family":"Xiong","sequence":"additional","affiliation":[{"name":"Artificial Intelligence & Computational Neuroscience Group (AICN Group), Sheffield Institute for Translational Neuroscience (SITraN), Division of Neuroscience, School of Medicine and Population Health, Faculty of Health, University of Sheffield, Sheffield S10 2HQ, UK"},{"name":"School of Information and Communication Engineering, Beijing University of Posts and Telecommunications, Beijing 100876, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graciela","family":"Muniz-Terrera","sequence":"additional","affiliation":[{"name":"Edinburgh Dementia Prevention, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK"},{"name":"Ohio University Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Edinburgh Dementia Prevention, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK"},{"name":"Scottish Brain Sciences, Edinburgh EH12 9DQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0837-5080","authenticated-orcid":false,"given":"John T.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Old Age Psychiatry Research Group (OAP Group), Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Su","sequence":"additional","affiliation":[{"name":"Artificial Intelligence & Computational Neuroscience Group (AICN Group), Sheffield Institute for Translational Neuroscience (SITraN), Division of Neuroscience, School of Medicine and Population Health, Faculty of Health, University of Sheffield, Sheffield S10 2HQ, UK"},{"name":"Old Age Psychiatry Research Group (OAP Group), Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SZ, UK"},{"name":"Insigneo Institute for In Silico Medicine, University of Sheffield, Sheffield S1 3JD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,3]]},"reference":[{"key":"ref_1","unstructured":"Prince, M., Wimo, A., Guerchet, M., Ali, G., Wu, Y., and Prina, M. 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