{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:18:16Z","timestamp":1784783896107,"version":"3.55.0"},"reference-count":83,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,7,27]],"date-time":"2025-07-27T00:00:00Z","timestamp":1753574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,7,27]],"date-time":"2025-07-27T00:00:00Z","timestamp":1753574400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obesity increases the risk for Alzheimer's disease (AD) and other dementias. Obesity causes structural brain injury, and it has been suggested that this may contribute to the development of AD pathology. Neurodegeneration in AD results from the aggregation of misfolded and dysfunctional tau and amyloid-\u03b2. However, it remains unknown whether adiposity-related brain injury acts through tau and amyloid deposition or as an independent cause of neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Here, we tested whether obesity, cerebrovascular disease, and obesity-related metabolic risk score were associated with structural brain and cognitive changes via the same mechanisms as AD or independent of them.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used the UK Biobank sample of over 33,000 individuals aged 64 years on average. We tested the influence of the microtubule-associated protein tau (\n                      <jats:italic>MAPT)<\/jats:italic>\n                      and apolipoprotein E (\n                      <jats:italic>APOE)<\/jats:italic>\n                      risk alleles involved in tau and amyloid-\u03b2 synthesis, folding, and clearance, as well as AD polygenic risk score (PRS) to define genetic risk of AD. Specifically, we investigated whether these genetic risk factors moderated the relationship between obesity and brain structure and cognition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that\n                      <jats:italic>MAPT<\/jats:italic>\n                      and\n                      <jats:italic>APOE<\/jats:italic>\n                      status and AD PRS did not moderate the relationship between obesity and brain atrophy. We also found limited evidence for the moderation of\n                      <jats:italic>MAPT<\/jats:italic>\n                      and\n                      <jats:italic>APOE<\/jats:italic>\n                      of the cerebrovascular disease-brain structure relationship as well as the metabolic risk score-brain structure relationship.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We conclude that the mechanisms linking obesity with brain atrophy are most likely independent of the ones governing AD-related protein deposition.<\/jats:p>\n                  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