{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:03:17Z","timestamp":1791295397335,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["UK DRI\u20103002"],"award-info":[{"award-number":["UK DRI\u20103002"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      The clusterin gene (\n                      <jats:italic>CLU<\/jats:italic>\n                      ) is a top genome\u2010wide association studies (GWAS) risk locus for Alzheimer's disease (AD) and elevated clusterin levels have been reported in AD biofluids and brain tissue. Despite growing interest in clusterin as a biomarker and therapeutic target, its cellular and subcellular localization in the human brain remains incompletely understood, in part due to a lack of well\u2010characterized reagents.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We generated and validated monoclonal antibodies (mAbs) that distinguish secreted and intracellular clusterin, and applied these tools to human biofluids, brain tissue, and induced pluripotent stem cell (iPSC) \u2010derived astrocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The mAbs enabled sensitive detection and quantification of clusterin in plasma, serum, cerebrospinal fluid, and brain tissue homogenates. Immunostaining demonstrated that clusterin is associated with amyloid plaques in AD brain and localizes to synapses in both healthy and AD tissue; the mAb detecting intracellular clusterin demonstrated specific expression in astrocytes, confirmed using astrocytoma lines and iPSC\u2010derived astrocytes. Quantitative analysis demonstrated increased clusterin signal in plaque\u2010associated astrocytes, particularly those surrounding larger plaques.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>The findings provide better understanding of clusterin expression in the healthy and AD brain, informing roles of clusterin in brain homeostasis and AD pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71885","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:37:06Z","timestamp":1791293826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clusterin is enriched in plaque\u2010associated astrocytes and localizes to synapses in Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Robert A. J.","family":"Byrne","sequence":"first","affiliation":[{"name":"UK Dementia Research Institute, School of Medicine Cardiff University  Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Veteleanu","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute, School of Medicine Cardiff University  Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah L.","family":"Cramp","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute, School of Medicine Cardiff University  Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia G.","family":"Bacon","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute, School of Medicine Cardiff University  Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten L.","family":"Baillie","sequence":"additional","affiliation":[{"name":"Hodge Centre for Translational Neuroscience, School of Medicine Cardiff University  Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Bright","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute, School of Medicine Cardiff University  Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah S.","family":"Cooke","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute, School of Medicine Cardiff University  Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth D.","family":"Fenn","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute, School of Medicine Cardiff University  Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Flores Castel\u00e1n","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute, School of Medicine Cardiff University  Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kok Yung","family":"Lee","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute, School of Medicine Cardiff University  Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wioleta M.","family":"Zelek","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute, School of Medicine Cardiff University  Cardiff Wales UK"},{"name":"Hodge Centre for Translational Neuroscience, School of Medicine Cardiff University  Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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