{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:56:37Z","timestamp":1790006197091,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","award":["UKDRI\u20103002"],"award-info":[{"award-number":["UKDRI\u20103002"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008897","name":"Janssen Pharmaceutica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dysregulation of the complement system plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). In post\u2010mortem AD brains, complement is deposited in and around amyloid plaques, and peri\u2010plaque complement activation drives synapse loss in AD mouse models. Studies to date have focused on amyloid pathology; however, aggregated tau is also involved in neuronal loss in AD. Primary tauopathies are characterised by tau pathology in the absence of amyloid. The role of complement in human tauopathies remains largely unexplored. Here, we address this knowledge gap by assessing complement activation in human tauopathy brains using immunohistochemistry and well\u2010characterised detection tools. Post\u2010mortem pre\u2010frontal cortex was obtained from three tauopathy subtypes, Pick's disease (PiD), globular glial tauopathy (GGT) and corticobasal degeneration (CBD) (3\u20135 cases each). C1q and the complement activation markers iC3b and terminal complement complex (TCC) were assessed by immunohistochemistry and were elevated in all tauopathy cases compared to controls, with C1q and C3b\/iC3b deposition particularly prominent on neurons, demonstrating complement activation on these cells. TCC deposits were present on and adjacent neurons in all tauopathy brains examined and were significantly increased compared to controls in CBD and GGT. Uniquely in GGT, abundant deposition of C3b\/iC3b on myelin was also observed, implicating complement in GGT\u2010associated demyelination. To validate these findings, complement proteins (C1q, C3, factor B), regulators (factor I, clusterin) and activation products (Ba, C3b\/iC3b, and TCC) were measured in brain homogenates by ELISA, revealing significant elevation in C3b\/iC3b, Ba, and FI in CBD and GGT cases compared to controls. Together, our data demonstrate complement activation on and adjacent neurons in post\u2010mortem brains from all tauopathy subtypes.<\/jats:p>","DOI":"10.1111\/bpa.70017","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T02:04:24Z","timestamp":1748311464000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Complement dysregulation in human tauopathies"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5793-1180","authenticated-orcid":false,"given":"Jacqui","family":"Nimmo","sequence":"first","affiliation":[{"name":"UK Dementia Research Institute Cardiff Cardiff University  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Keat","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute Cardiff Cardiff University  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"De Muynck","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development Janssen Pharmaceutica NV, a Johnson &amp; Johnson Company  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4075-7676","authenticated-orcid":false,"given":"B. 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