{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:04:25Z","timestamp":1788959065540,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Multiple system atrophy (MSA) is characterized by neuronal loss with gliosis in the striatonigral and olivopontocerebellar structures, along with phosphorylated \u03b1\u2010synuclein accumulation in oligodendroglias and neurons. Although subpial and subependymal astrocytic \u03b1\u2010synuclein accumulation has been reported in cases of long\u2010duration MSA, little is known regarding cerebral cortical astrocytic \u03b1\u2010synuclein pathology in MSA. A 61\u2010year\u2010old woman developed dizziness and dysarthria at 38\u2009years of age. She was diagnosed with MSA\u2010C based on the typical neurological and imaging findings of MSA. Tracheostomy was performed at 48\u2009years of age. Voluntary movement disappeared completely at 49\u2009years of age. The patient died at age 61. The overall clinical course of the MSA was 22\u2009years. The brain, weighing 780\u2009g after fixation, showed severe atrophy, with discoloration of the brainstem, cerebellum, basal ganglia, cerebral cortex, and cerebral white matter. The substantia nigra and locus ceruleus had severe depigmentation. Microscopically, the frontotemporal regions of the cerebral cortices, striatum, pontine nucleus, inferior olivary nuclei, cerebellar white matter, and Purkinje cells had severe degeneration. The widespread occurrence of phosphorylated \u03b1\u2010synuclein\u2010positive neuronal and oligodendroglial inclusions, such as glial cytoplasmic inclusions, is noteworthy, leading to a definite diagnosis of MSA. Regarding astrocytic lesions, astrocyte processes\u2010dominant \u03b1\u2010synuclein accumulation in the cerebral cortices and amygdaloid nucleus was observed. Furthermore, several astrocytes in the cerebral white matter showed \u03b1\u2010synuclein\u2010positive inclusions in the periphery of the cytoplasm and proximal parts of the processes besides \u03b1\u2010synuclein\u2010positive subpial astrocytes in the ventral part of the brainstem. The atypical form of \u03b1\u2010synuclein and advanced propagation of the pathogenic protein induced by a long clinical course can be implicated in the astrocytic cytopathology of MSA.<\/jats:p>","DOI":"10.1111\/neup.70026","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T01:03:46Z","timestamp":1758848626000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cerebral Astrocytic Phosphorylated\u2010\u03b1\u2010Synuclein Accumulation in Multiple System Atrophy With Long Clinical Course"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8865-4097","authenticated-orcid":false,"given":"Kenji","family":"Sakai","sequence":"first","affiliation":[{"name":"Department of Neurology Joetsu General Hospital  Joetsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2007.00841.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12243"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-002-0655-0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181b66f1b"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-01977-2"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-025-01944-x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-004-0935-y"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-020-0185-5"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12362"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.13002"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29005"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.3A6213.2004"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2006.00713.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.081125"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-019-0703-9"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1746-2"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae137"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010000292"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1442-z"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12289"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12783"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.02.009"}],"container-title":["Neuropathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/neup.70026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:28:10Z","timestamp":1759796890000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/neup.70026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/neup.70026"],"URL":"https:\/\/doi.org\/10.1111\/neup.70026","archive":["Portico"],"relation":{},"ISSN":["0919-6544","1440-1789"],"issn-type":[{"value":"0919-6544","type":"print"},{"value":"1440-1789","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,25]]},"assertion":[{"value":"2025-07-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70026"}}