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In this multicentre study, we measured plasma phosphorylated-tau217 in controls (n = 60), Niemann\u2013Pick disease type C (n = 71) and Alzheimer\u2019s disease (n = 30 positive for amyloid and negative for tau in CSF [A+T\u2212] and n = 30 positive for both [A+T+]). Annual Severity Increment Score and Lysotracker measurements were evaluated in the Niemann\u2013Pick disease type C group to estimate the rate of progression and lysosomal enlargement, respectively. In the cross-sectional analysis, plasma phosphorylated-tau217 was increased in Niemann\u2013Pick disease type C compared with controls (2.52 \u00b1 1.93 versus 1.02 \u00b1 0.34\u2005pg\/mL, respectively, P &amp;lt; 0.001) and inversely correlated with age at disease onset (R = \u22120.54, P &amp;lt; 0.001). In the longitudinal analysis, plasma phosphorylated-tau217 was associated with disease progression determined by Annual Severity Increment Score (R = 0.48, P &amp;lt; 0.001) and lysosomal enlargement (R = 0.26, P = 0.004). We found no differences between A+T\u2212 Alzheimer\u2019s disease and Niemann\u2013Pick disease type C (2.67 \u00b1 1.18 versus 2.52 \u00b1 1. 93\u2005pg\/mL, P = 0.31); however, A+T+ Alzheimer\u2019s disease had significantly higher levels than Niemann\u2013Pick disease type C (3.26 \u00b1 1.36 versus 2.52 \u00b1 1.93\u2005pg\/mL, P = 0.001). Our findings suggest that plasma p-tau217 can increase in brain disorders with isolated tau pathology. Plasma p-tau217 associations with disease progression and severity make it a potential marker in Niemann\u2013Pick disease type C.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae375","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T08:11:02Z","timestamp":1729843862000},"source":"Crossref","is-referenced-by-count":17,"title":["Plasma phosphorylated-tau217 is increased in Niemann\u2013Pick disease type C"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7897-9456","authenticated-orcid":false,"given":"Fernando","family":"Gonzalez-Ortiz","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal, 43180 ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , M\u00f6lndal, 43180 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1422-4358","authenticated-orcid":false,"given":"Thomas K","family":"Karikari","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal, 43180 ,","place":["Sweden"]},{"name":"Department of Psychiatry, School of Medicine, University of Pittsburgh , Pittsburgh, PA 15203 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Taylor-Te Vruchte","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford , Oxford OX1 3QT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn","family":"Shepherd","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford , Oxford OX1 3QT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1413-9578","authenticated-orcid":false,"given":"Bj\u00f8rn-Eivind","family":"Kirsebom","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of North Norway , Troms\u00f8, 9019 ,","place":["Norway"]},{"name":"Department of Psychology, Faculty of Health Sciences, The Arctic University of Norway , Troms\u00f8, 9031 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tormod","family":"Fladby","sequence":"additional","affiliation":[{"name":"Department of Neurology, Akershus University Hospital , L\u00f8renskog, 1478 ,","place":["Norway"]},{"name":"Institute of Clinical Medicine, Campus Ahus, University of Oslo , Oslo, 0316 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