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We examined whether astrocyte reactivity modulates the relationship between LC dysfunction, tau pathology, and cognitive decline in humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We combined ultra\u2010high\u2010field LC functional imaging during an affective task with plasma biomarkers of glial fibrillary acidic protein (GFAP) and hyperphosphorylated tau (p\u2010tau), and longitudinal cognitive data from 78 asymptomatic individuals. Associations between LC activity and norepinephrine transporter\u2010enriched LC functional connectivity (LCFC) with p\u2010tau, GFAP, and cognitive decline were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Lower LC activity and LCFC were related to elevated plasma p\u2010tau\n                      <jats:sub>217<\/jats:sub>\n                      , particularly at elevated GFAP. Lower LC FC was also associated with cognitive decline in individuals with elevated plasma p\u2010tau\n                      <jats:sub>217<\/jats:sub>\n                      and GFAP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>LC\u2013norepinephrine system dysfunction may contribute to emerging tau pathology and cognitive decline, with astrocytes playing a critical gating role.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71703","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T15:04:45Z","timestamp":1785942285000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Astrocyte reactivity modifies the effects of locus coeruleus norepinephrine\u2010related dysfunction on tau and its impact on cognition"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5444-8359","authenticated-orcid":false,"given":"Prokopis C.","family":"Prokopiou","sequence":"first","affiliation":[{"name":"Athinoula A. 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