{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:47:14Z","timestamp":1790293634792,"version":"4.1.0"},"reference-count":75,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Alzheimer's disease features\u00a0early a pathology in the locus coeruleus (LC), yet how sex and life experience shape LC vulnerability remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We expressed pseudophosphorylated human tau (htauE14) in LC neurons of TH\u2010Cre rats and exposed both sexes to early\u2010 or late\u2010life enrichment or stress. Behavioral, histological, protein, and hippocampal single\u2010nucleus RNA sequencing (snRNA\u2010seq) analyses were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>LC\u2010targeted htauE14 impaired learning and increased anxiety\u2010like behavior. Early enrichment reduced htauE14 spread and LC microglia activation, elevated hippocampal brain\u2010derived neurotrophic factor (BDNF), and improved olfactory learning in males. Late enrichment alleviated anxiety and enhanced spatial memory, whereas late stress exacerbated LC degeneration. Hippocampal snRNA\u2010seq revealed sex\u2010 and cell type\u2013specific transcriptional responses, with htauE14 preferentially engaging metabolic and synaptic pathways in females, effects amplified by early stress but stabilized by early enrichment. Late\u2010life experiences primarily recruited homeostatic regulatory programs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Sex and developmental history critically shape early LC tau\u2010related vulnerability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71285","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T09:37:46Z","timestamp":1773135466000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sex and life experience shape locus coeruleus pretangle tau pathology"],"prefix":"10.1002","volume":"22","author":[{"given":"Zia","family":"Hasan","sequence":"first","affiliation":[{"name":"Biomedical Sciences Faculty of Medicine Memorial University of Newfoundland  St. John's Newfoundland and Labrador Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Torraville","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Faculty of Medicine Memorial University of Newfoundland  St. John's Newfoundland and Labrador Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamunotonye","family":"Omoluabi","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Faculty of Medicine Memorial University of Newfoundland  St. John's Newfoundland and Labrador Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Maziar","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Faculty of Medicine Memorial University of Newfoundland  St. John's Newfoundland and Labrador Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onyedikachi N.","family":"Belolise","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Faculty of Medicine Memorial 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