{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:40:47Z","timestamp":1791999647442,"version":"4.4.0"},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T00:00:00Z","timestamp":1551916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:p>Sporadic prion diseases are fatal neurodegenerative disorders characterized clinically by rapidly progressive dementia and myoclonus. Variably protease\u2010sensitive prionopathy (VPSPr) is a recently identified sporadic human prion disorder that may present with a lengthy atypical clinical history. Here, we describe a case of VPSPr in a patient with a long history of suspected frontotemporal dementia (FTD). A 61\u2010year\u2010old man presented with speech difficulties, including naming objects and constructing multipart sentences, while there was no difficulty in comprehension. Movement abnormalities included slightly jerky pursuit, minor dysmetria of saccades and brisk reflexes. There was no family history of dementia. Later he developed swallowing difficulties and the possibility of FTD with motor neuron disease was suspected. He died at the age of 71 and his brain was donated to the London Neurodegenerative Diseases Brain Bank. The brain (1004 g) showed mild to moderate atrophy, predominantly in the frontal lobe. Histology revealed moderate spongiform microvacuolation mostly affecting the frontal and parietal cortices, but also present focally in the basal ganglia and the cerebellum. Only mild Alzheimer pathology was found by extensive immunohistochemistry, in keeping with BrainNet Europe stage II. Trans\u2010activation response DNA\u2010binding protein 43 kDa and \u03b1\u2010synuclein immunostains were negative. Immunostaining for prion protein (PrP) showed granular\/synaptic positivity in a patchy distribution, mainly within the deeper cortex, and also revealed microplaques in the cerebellum and basal ganglia. Western blotting confirmed a low molecular weight protease\u2010resistant PrP band with a faint ladder\u2010like pattern in the absence of types 1 and 2 isoforms. These features are diagnostic of VPSPr. VPSPr can mimic various neurodegenerative conditions; diagnosis requires both PrP immunohistochemistry and Western blotting. The presence of patchy spongiform change in the absence of other neurodegenerative pathology should raise suspicion of VPSPr, even in elderly patients with a lengthy clinical history.<\/jats:p>","DOI":"10.1111\/neup.12538","type":"journal-article","created":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T06:59:39Z","timestamp":1552028379000},"page":"135-140","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Variably protease\u2010sensitive prionopathy mimicking frontotemporal dementia"],"prefix":"10.1111","volume":"39","author":[{"given":"Miren","family":"Aizpurua","sequence":"first","affiliation":[{"name":"Clinical Neuropathology King's College Hospital, NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sashika","family":"Selvackadunco","sequence":"additional","affiliation":[{"name":"London Neurodegenerative Diseases Brain Bank IOPPN  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Yull","sequence":"additional","affiliation":[{"name":"National Creutzfeldt\u2010Jakob Disease Research &amp; Surveillance Unit, Centre for Clinical Brain Sciences University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Kipps","sequence":"additional","affiliation":[{"name":"Wessex Neurological Centre University Hospital Southampton NHS Foundation Trust  Southampton UK"},{"name":"Clinical Neurosciences University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Ironside","sequence":"additional","affiliation":[{"name":"National Creutzfeldt\u2010Jakob Disease Research &amp; Surveillance Unit, Centre for Clinical Brain Sciences University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2533-4758","authenticated-orcid":false,"given":"Istvan","family":"Bodi","sequence":"additional","affiliation":[{"name":"Clinical Neuropathology King's College Hospital, NHS Foundation Trust  London UK"},{"name":"London Neurodegenerative Diseases Brain Bank IOPPN  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6815801"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0585-1"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390613"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199908)46:2<224::AID-ANA12>3.0.CO;2-W"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21420"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22094"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1309-8"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2009.01040.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0766-y"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws366"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036333"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-309871"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-10-99"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-1947-6-348"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.632"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63945-5.00010-6"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-011-9543-1"}],"container-title":["Neuropathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fneup.12538","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/neup.12538","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/neup.12538","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/neup.12538","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T20:53:05Z","timestamp":1694379185000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/neup.12538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,7]]},"references-count":17,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1111\/neup.12538"],"URL":"https:\/\/doi.org\/10.1111\/neup.12538","archive":["Portico"],"relation":{},"ISSN":["0919-6544","1440-1789"],"issn-type":[{"value":"0919-6544","type":"print"},{"value":"1440-1789","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,7]]},"assertion":[{"value":"2018-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}