{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T06:14:55Z","timestamp":1787206495298,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,8,25]],"date-time":"2019-08-25T00:00:00Z","timestamp":1566691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 NS084974"],"award-info":[{"award-number":["P01 NS084974"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 AG016574"],"award-info":[{"award-number":["P50 AG016574"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35 NS097261"],"award-info":[{"award-number":["R35 NS097261"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35 NS097273"],"award-info":[{"award-number":["R35 NS097273"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify clinicopathological differences between frontotemporal lobar degeneration (FTLD) due to mutations in progranulin (FTLD\u2010GRN) and chromosome 9 open reading frame 72 (FTLD\u2010C9ORF72).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed quantitative neuropathologic comparison of 17 FTLD\u2010C9ORF72 and 15 FTLD\u2010GRN with a focus on microglia. For clinical comparisons, only cases with high quality medical documentation and concurring diagnoses by at least two neurologists were included (14\u00a0FTLD\u2010GRN and 13 FTLD\u2010C9ORF72). Neuropathological analyses were limited to TDP\u201043 Type A to assure consistent assessment between the groups, acknowledging that Type A is a minority of C9ORF72 patients. Furthermore, only cases with sufficient tissue from all regions were studied (11 FTLD\u2010GRN and 11 FTLD\u2010C9ORF72). FTLD cases were also compared to age\u2013 and sex\u2013matched normal controls. Immunohistochemistry was performed for pTDP\u201043, IBA\u20101, CD68, and GFAP. Morphological characterization of microglia was performed in sections of cortex blinded to clinical and genetic information.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>FTLD\u2010GRN patients had frequent asymmetric clinical features, including aphasia and apraxia, as well as more asymmetric cortical atrophy. Neuropathologically, FTLD\u2010C9ORF72 had greater hippocampal tau pathology and more TDP\u201043 neuronal cytoplasmic inclusions. FTLD\u2010GRN had more neocortical microvacuolation, as well as more IBA\u20101\u2013positive ameboid microglia in superficial cortical layers and in subcortical white matter. FTLD\u2010GRN also had more microglia with nuclear condensation, possibly indicating apoptosis. Microglial morphology with CD68 immunohistochemistry in FTLD\u2010GRN and FTLD\u2010C9ORF72 differed from controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our findings underscore differences in microglial response in FTLD\u2010C9ORF72 and FTLD\u2010GRN as shown by significant differences in ameboid microglia in gray and white matter. These results suggest the differential contribution of microglial dysfunction in FTLD\u2010GRN and FTLD\u2010C9ORF72 and suggest that clinical, neuroimaging and pathologic differences could in part be related to differences in microglia response.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50875","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T01:28:56Z","timestamp":1566782936000},"page":"1782-1796","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Microglia in frontotemporal lobar degeneration with progranulin or C9ORF72 mutations"],"prefix":"10.1002","volume":"6","author":[{"given":"Nobutaka","family":"Sakae","sequence":"first","affiliation":[{"name":"Department of Neuroscience Mayo Clinic Jacksonville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanu F.","family":"Roemer","sequence":"additional","affiliation":[{"name":"Department of Neuroscience 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