{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:27:46Z","timestamp":1793500066594,"version":"4.5.0"},"reference-count":80,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010969","name":"Alzheimer Nederland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010969","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A subpopulation of astrocytes expressing WD Repeat Domain 49 (WDR49) was recently identified in frontotemporal lobar degeneration (FTLD) with\n                    <jats:italic>GRN<\/jats:italic>\n                    pathogenic variants. This is the first study to investigate their expression and relation to pathology in other FTLD subtypes and Alzheimer's disease (AD). In a\n                    <jats:italic>postmortem<\/jats:italic>\n                    cohort of TDP\u201043 proteinopathies (12\n                    <jats:italic>GRN<\/jats:italic>\n                    , 11\n                    <jats:italic>C9orf72<\/jats:italic>\n                    , 9 sporadic TDP\u201043), tauopathies (13\n                    <jats:italic>MAPT<\/jats:italic>\n                    , 8 sporadic tau), 10 AD, and four controls, immunohistochemistry and immunofluorescence were performed for WDR49 and pathological inclusions on frontal, temporal, and occipital cortical sections. WDR49\u2010positive cell counts (adjusted per mm\n                    <jats:sup>2<\/jats:sup>\n                    ) were examined and related to digitally quantified percentage areas of TDP\u201043\/tau pathology and semiquantitative scores of neurodegeneration. Quantitative colocalization analysis of WDR49 and pathological inclusions was done. WDR49\u2010positive astrocytes were present across FTLD subtypes and AD in the brain parenchyma and (peri\u2010)vascular space, with distinct morphological patterns, and were particularly enriched in gray matter. In controls, sporadic WDR49\u2010positive cells were found enveloping vessels. WDR49\u2010positive astrocytes were most abundant in the frontal cortex (FC)\u00a0of\n                    <jats:italic>GRN<\/jats:italic>\n                    cases and temporal cortex in\n                    <jats:italic>GRN<\/jats:italic>\n                    , AD, and sporadic primary tauopathy. In the occipital cortex, only a few cells were found across groups. WDR49\u2010positive astrocyte counts positively correlated with the severity of neurodegeneration and TDP\u201043 pathology but not tauopathy. Furthermore, in frontotemporal cortices, WDR49 partly colocalized with TDP\u201043 (14%\u201321%) and tau (31%\u201345%). In conclusion, WDR49 is a marker for a subset of astrocytes with different morphologies across FTLD and AD, reflecting the severity of neurodegeneration. These astrocytes may become activated in neurodegeneration in response to pathological damage and migrate from the vessel wall to the parenchyma.\n                  <\/jats:p>","DOI":"10.1002\/glia.24663","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T13:05:37Z","timestamp":1734699937000},"page":"948-968","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>WDR49<\/scp>\n                    \u2010Positive Astrocytes Mark Severity of Neurodegeneration in Frontotemporal Lobar Degeneration\u00a0and Alzheimer's Disease"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6399-8170","authenticated-orcid":false,"given":"Ana","family":"Rajicic","sequence":"first","affiliation":[{"name":"Department of Neurology and Alzheimer Centre Erasmus MC Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia A. A.","family":"Giannini","sequence":"additional","affiliation":[{"name":"Department of Neurology and Alzheimer Centre Erasmus MC Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Gerrits","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"van Buuren","sequence":"additional","affiliation":[{"name":"Department of Neurology and Alzheimer Centre Erasmus MC Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamiram","family":"Melhem","sequence":"additional","affiliation":[{"name":"Department of Neurology and Alzheimer Centre Erasmus MC Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan A.","family":"Slotman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Erasmus Optical Imaging Center Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke J. M.","family":"Rozemuller","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam Neuroscience Amsterdam University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8941-0353","authenticated-orcid":false,"given":"Bart J. 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