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However, the effects of age and sex on AMPAR distribution in the living human brain and their associations with cognitive function remain unclear. The purpose of this study was to characterize age- and sex-dependent changes in brain AMPAR density and their relationships with cognitive performance in healthy individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using a positron emission tomography tracer for AMPAR, [\n                      <jats:sup>11<\/jats:sup>\n                      C]K-2, we imaged 143 healthy participants aged 20\u201379\u00a0years. AMPAR density was evaluated using standard uptake value ratios with white matter as a reference. Age- and sex-related changes in AMPAR density were assessed across the brain, hierarchical clustering was used to characterize sex-dependent regional patterns of age-related change, and associations with cognitive performance were examined using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Age-dependent differences in cell-surface AMPAR density was observed across most brain regions. Females in their 50\u00a0s showed a surge in the upregulation of AMPAR density across brain. Hierarchical clustering revealed five distinct age-related trajectories, featuring marked sex-dependent regional patterns. AMPAR density was positively associated with cognitive performance; delayed memory correlated with whole-brain AMPAR density in both sexes, whereas other cognitive domains showed sex-specific regional associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings demonstrated age- and sex-related alteration of AMPAR distribution and propose a model of AMPAR related synaptic aging in the living human brain over the life span. Furthermore, they may help to elucidate the pathophysiology of neurodegenerative disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-07963-7","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T16:02:17Z","timestamp":1782144137000},"page":"6299-6310","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age and sex-dependent alteration in AMPA receptor density in living human brain"],"prefix":"10.1007","volume":"53","author":[{"given":"Mai","family":"Hatano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waki","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Tsuchimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsu","family":"Arisawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuuki","family":"Takada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Eiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadamitsu","family":"Ichijo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akane","family":"Sano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shariful A.","family":"Syed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Tani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruki","family":"Koizumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kie","family":"Nomoto-Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Ohtani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Jinzaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoji","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Mitoma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Tamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Baba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Togao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Kosaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidehiko","family":"Okazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Mimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6523-0622","authenticated-orcid":false,"given":"Takuya","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"7963_CR1","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/0197-4580(87)90024-8","volume":"8","author":"GB Freeman","year":"1987","unstructured":"Freeman GB, Gibson GE. 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The Yokohama City University Human Investigation Committee and the Certified Institutional Review Board approved each study. The Ethical Guidelines for Medical and Health Research Involving Human Participants set by the Japan Ministry of Health, Labour and Welfare, as well as the Clinical Trials Act in Japan, were adhered to in each study.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":2,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All participants provided written informed consent for the publication of anonymized images and relevant data included in this article.","order":3,"name":"Ethics","label":"Consent to publish","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Takuya Takahashi is the inventors of a patent application for a novel compound that specifically binds to the AMPA receptor (WO 2017006931), including [\n                      11\n                      C]K-2. Takuya Takahashi and Tetsu Arisawa are the founders and also stockholders of AMPAMETRY, Inc., which holds the exclusive license to use [\n                      11\n                      C]K-2. No other potential conflicts of interest relevant to this article exist.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}