{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T15:07:52Z","timestamp":1740150472107,"version":"3.37.3"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K06887","22H02948"],"award-info":[{"award-number":["20K06887","22H02948"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Collaborative Research Project of the Brain Research Institute"},{"DOI":"10.13039\/100012833","name":"Niigata University","doi-asserted-by":"publisher","award":["201909"],"award-info":[{"award-number":["201909"]}],"id":[{"id":"10.13039\/100012833","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21wm0425019"],"award-info":[{"award-number":["JP21wm0425019"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Karouji Memorial Fund for Medical Research in Hirosaki University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder pathologically characterized by the presence of glial cytoplasmic inclusions (GCIs). Some MSA patients exhibit motor deficits with accompanying cognitive impairment. Of note, some patients suffering from MSA with longer disease duration have AT8-positive signals, which correspond to phosphorylated tau (P-tau) at 202\/205 (P-tau202\/205). However, P-tau sites other than the AT8 antibody epitope antibody are less well studied. Here, we focused on the effect of \u03b1-synuclein (Syn) expression on the phosphorylation of tau in MSA model mice. Among the 6 kinds of antibodies against P-tau, we confirmed that antibodies against P-tau at 231 (P-tau231) were phospho-specific and found that P-tau231 level was increased in parallel with disease progression in MSA model mice. Additional studies of human brains revealed that P-tau231 was mainly expressed in the temporal cortex in MSA brains and that its expression level was significantly higher in MSA patients than in controls. Immunohistochemical analysis showed that anti-P-tau231-, but not AT8, antibodies mainly immunolabeled hippocampal CA2\/3 pyramidal neurons, and some GCIs in MSA. These data suggest that P-tau231 occurs in MSA differently from P-tau202\/205.<\/jats:p>","DOI":"10.1093\/jnen\/nlac082","type":"journal-article","created":{"date-parts":[[2022,9,10]],"date-time":"2022-09-10T00:08:11Z","timestamp":1662768491000},"page":"920-930","source":"Crossref","is-referenced-by-count":1,"title":["Phosphorylation of Tau at Threonine 231 in Patients With Multiple System Atrophy and in a Mouse Model"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4037-3795","authenticated-orcid":false,"given":"Makoto T","family":"Tanaka","sequence":"first","affiliation":[{"name":"From the Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine , Hirosaki, Japan"},{"name":"Department of Biological Science, Graduate School of Science and Engineering, Iwate University , Morioka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunikazu","family":"Tanji","sequence":"additional","affiliation":[{"name":"From the Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine , Hirosaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuo","family":"Miki","sequence":"additional","affiliation":[{"name":"From the Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine , Hirosaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Graduate School of Science and Engineering, Iwate University , Morioka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiaki","family":"Mori","sequence":"additional","affiliation":[{"name":"From the Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine , Hirosaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Hayashi","sequence":"additional","affiliation":[{"name":"From the Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine , Hirosaki, Japan"},{"name":"Department of Pathology, Brain Research Institute, Niigata University , Niigata, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiyoshi","family":"Kakita","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brain Research Institute, Niigata University , Niigata, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Wakabayashi","sequence":"additional","affiliation":[{"name":"From the Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine , Hirosaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"2024032523480777200_nlac082-B1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/ncb748","article-title":"Alpha-synuclein is phosphorylated in synucleinopathy lesions","volume":"4","author":"Fujiwara","year":"2002","journal-title":"Nat Cell Biol"},{"key":"2024032523480777200_nlac082-B2","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1097\/00005072-199009000-00007","article-title":"Oligodendroglial microtubular tangles in olivopontocerebellar atrophy","volume":"49","author":"Nakazato","year":"1990","journal-title":"J Neuropathol Exp Neurol"},{"key":"2024032523480777200_nlac082-B3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0022-510X(89)90219-0","article-title":"Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome)","volume":"94","author":"Papp","year":"1989","journal-title":"J Neurol Sci"},{"key":"2024032523480777200_nlac082-B4","doi-asserted-by":"crossref","first-page":"48984","DOI":"10.1074\/jbc.M208194200","article-title":"Golgi fragmentation occurs in the cells with prefibrillar alpha-synuclein aggregates and precedes the formation of fibrillar inclusion","volume":"277","author":"Gosavi","year":"2002","journal-title":"J Biol Chem"},{"key":"2024032523480777200_nlac082-B5","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1126\/science.1082324","article-title":"Initiation and synergistic fibrillization of tau and alpha-synuclein","volume":"300","author":"Giasson","year":"2003","journal-title":"Science"},{"key":"2024032523480777200_nlac082-B6","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1111\/jnc.15257","article-title":"Alpha-synuclein abnormalities trigger focal tau pathology, spreading to various brain areas in Parkinson disease","volume":"157","author":"Hadi","year":"2021","journal-title":"J Neurochem"},{"key":"2024032523480777200_nlac082-B7","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1111\/j.1460-9568.2011.07660.x","article-title":"Hyperphosphorylated tau in an alpha-synuclein-overexpressing transgenic model of Parkinson\u2019s disease","volume":"33","author":"Haggerty","year":"2011","journal-title":"Eur J Neurosci"},{"key":"2024032523480777200_nlac082-B8","doi-asserted-by":"crossref","first-page":"117010","DOI":"10.1016\/j.jns.2020.117010","article-title":"Cerebral white matter tau-positive granular glial pathology as a characteristic pathological feature in long survivors of multiple system atrophy","volume":"416","author":"Homma","year":"2020","journal-title":"J Neurol Sci"},{"key":"2024032523480777200_nlac082-B9","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/j.1440-1789.2011.01246.x","article-title":"Unusual tau in 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initial stages of the preclinical Alzheimer\u2019s continuum when only subtle changes in Abeta pathology are detected","volume":"12","author":"Su\u00e1rez-Calvet","year":"2020","journal-title":"EMBO Mol Med"},{"key":"2024032523480777200_nlac082-B34","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s00401-021-02275-6","article-title":"Plasma p-tau231: A new biomarker for incipient Alzheimer\u2019s disease pathology","volume":"141","author":"Ashton","year":"2021","journal-title":"Acta Neuropathol"}],"container-title":["Journal of Neuropathology &amp; Experimental 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