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Yet, these biomarkers identify two distinct A\u03b2 pools, reflecting the clearance of soluble A\u03b2 as opposed to the presence of A\u03b2 fibrils in the brain. An open question is whether risk factors known to increase Alzheimer\u2019s\u2019 disease (AD) prevalence may promote an imbalance between soluble and deposited A\u03b2. Unveiling such interactions shall aid our understanding of the biological pathways underlying A\u03b2 deposition and foster the design of effective prevention strategies. We assessed the impact of three major AD risk factors, such as age,\n                    <jats:italic>APOE<\/jats:italic>\n                    -\u03b54 and female sex, on the association between CSF and PET A\u03b2, in two independent samples of non-demented individuals (ALFA:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009320, ADNI:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009682). We tested our hypotheses both in candidate regions of interest and in the whole brain using voxel-wise non-parametric permutations. All of the assessed risk factors induced a higher A\u03b2 deposition for any given level of CSF A\u03b242\/40, although in distinct cerebral topologies. While age and sex mapped onto neocortical areas, the effect of\n                    <jats:italic>APOE<\/jats:italic>\n                    -\u03b54 was prominent in the medial temporal lobe, which represents a target of early tau deposition. Further, we found that the effects of age and\n                    <jats:italic>APOE<\/jats:italic>\n                    -\u03b54 was stronger in women than in men. Our data indicate that specific AD risk factors affect the spatial patterns of cerebral A\u03b2 aggregation, with\n                    <jats:italic>APOE<\/jats:italic>\n                    -\u03b54 possibly facilitating a co-localization between A\u03b2 and tau along the disease\n                    <jats:italic>continuum<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41380-022-01436-7","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T10:02:37Z","timestamp":1646215357000},"page":"2010-2018","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Age, sex and APOE-\u03b54 modify the balance between soluble and fibrillar \u03b2-amyloid in non-demented individuals: topographical patterns across two independent 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MSC has given lectures in symposia sponsored by ROCHE DIAGNOSTICS, S.L.U. GK is a full-time employee of Roche Diagnostics GmbH. IS is a full-time employee and shareholder of Roche Diagnostics International Lda. HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). The rest of the authors have no conflict of interest to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}