{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T17:18:04Z","timestamp":1764350284075},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T00:00:00Z","timestamp":1434585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Labour and Welfare of Japan, the Science Research Promotion Fund, Promotion and Mutual Aid Corporation for Private Schools of Japan, and the JSPS KAKENHI","award":["C25430054"],"award-info":[{"award-number":["C25430054"]}]},{"name":"BioBank of the National Center for Geriatrics and Gerontology","award":["NCGG 26-20"],"award-info":[{"award-number":["NCGG 26-20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:p>Nasu\u2010Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by formation of multifocal bone cysts and development of leukoencephalopathy, caused by genetic mutations of either DNAX\u2010activation protein 12 (<jats:italic>DAP12<\/jats:italic>) or triggering receptor expressed on myeloid cells 2 (<jats:italic>TREM2<\/jats:italic>). Although increasing evidence suggests a defect in microglial TREM2\/DAP12 function in NHD, the molecular mechanism underlying leukoencephalopathy with relevance to microglial dysfunction remains unknown. TREM2, by transmitting signals via the immunoreceptor tyrosine\u2010based activation motif (ITAM) of DAP12, stimulates phagocytic activity of microglia, and ITAM signaling is counterbalanced by sialic acid\u2010binding immunoglobulin (Ig)\u2010like lectins (Siglecs)\u2010mediated immunoreceptor tyrosine\u2010based inhibitory motif (ITIM) signaling. To investigate a role of CD33, a member of the Siglecs family acting as a negative regulator of microglia activation, in the pathology of NHD, we studied CD33 expression patterns in five NHD brains and 11 controls by immunohistochemistry. In NHD brains, CD33 was identified exclusively on ramified and amoeboid microglia accumulated in demyelinated white matter lesions but not expressed in astrocytes, oligodendrocytes, or neurons. However, the number of CD33\u2010immunoreactive microglia showed great variability from case to case and from lesion to lesion without significant differences between NHD and control brains. These results do not support the view that CD33\u2010expressing microglia play a central role in the development of leukoencephalopathy in NHD brains.<\/jats:p>","DOI":"10.1111\/neup.12222","type":"journal-article","created":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T10:34:08Z","timestamp":1434623648000},"page":"529-537","source":"Crossref","is-referenced-by-count":8,"title":["Immunohistochemical characterization of CD33 expression on microglia in Nasu\u2010Hakola disease brains"],"prefix":"10.1111","volume":"35","author":[{"given":"Jun\u2010ichi","family":"Satoh","sequence":"first","affiliation":[{"name":"Department of Bioinformatics and Molecular Neuropathology Meiji Pharmaceutical University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Kino","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Molecular Neuropathology Meiji Pharmaceutical University  Tokyo 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