{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T11:41:38Z","timestamp":1772710898404,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K07097"],"award-info":[{"award-number":["17K07097"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Genetic Creutzfeldt\u2013Jakob disease (gCJD) with V180I prion protein gene (<jats:italic>PRNP<\/jats:italic>) mutation shows weaker prion protein (PrP) deposition histologically compared with sporadic CJD, and it is more difficult to detect protease\u2010resistant prion protein in immunoblotting. However, we previously reported the autopsy case of a patient with V180I gCJD who was treated with pentosan polysulfate sodium (PPS); this case had increased protease\u2010resistant PrP deposition. It has been suggested that PPS might reduce protease\u2010resistant PrP; however, the detailed pharmacological and histopathological effects of PPS in humans remain unknown. We examined autopsied human brain tissue from four cases with V180I gCJD that were added to our archives between 2011 and 2021: two cases treated with PPS and two cases without PPS. We conducted a neuropathological assessment, including immunohistochemistry for PrP. We also performed immunoblotting for PrP on homogenate samples from each brain to detect protease\u2010resistant PrP using both a conventional procedure and size\u2010exclusion gel chromatography for the purification of oligomeric PrP. Both PPS\u2010treated cases showed long survival time over 5\u2009years from onset and increased PrP deposition with a characteristic pattern of coarse granular depositions and congophilic PrP microspheres, whereas the cases without PPS showed around 1\u2010year survival from onset and relatively mild neuronal loss and synaptic PrP deposition. Although cortical gliosis seemed similar among all cases, aquaporin 4\u2010expression as a hallmark of astrocytic function was increased predominantly in PPS cases. Immunoblotting of non\u2010PPS cases revealed protease\u2010resistant PrP in the oligomeric fraction only, whereas the PPS\u2010treated cases showed clear signals using conventional procedures and in the oligomeric fraction. These unique biochemical and histopathological changes may reflect the progression of V180I gCJD and its modification by PPS, suggesting the possible existence of toxic PrP\u2010oligomer in the pathophysiology of V180I gCJD and beneficial effects of PPS toward the aggregation and detoxication of toxic PrP\u2010oligomer.<\/jats:p>","DOI":"10.1111\/bpa.13197","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T04:42:59Z","timestamp":1690864979000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Altered properties of amyloidogenic prion protein in genetic <scp>Creutzfeldt\u2013Jakob<\/scp> disease with <scp><i>PRNP<\/i> V180I<\/scp> mutation in response to pentosan polysulfate"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6851-2860","authenticated-orcid":false,"given":"Masahiro","family":"Shijo","sequence":"first","affiliation":[{"name":"Department of Neuropathology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"},{"name":"Department of Internal Medicine Fukuoka Dental College Medical and Dental Hospital  Fukuoka Japan"},{"name":"Department of Neurology Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motoi","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuyoshi","family":"Omae","sequence":"additional","affiliation":[{"name":"Department of Medicine Imazu Red Cross Hospital  Fukuoka 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