Fernando Gonzalez-Ortiz, Thomas K Karikari, Danielle Taylor-Te Vruchte, Dawn Shepherd, Bjørn-Eivind Kirsebom, Tormod Fladby, Frances Platt, Kaj Blennow
{"title":"Plasma phosphorylated-tau217 is increased in Niemann-Pick disease type C.","authors":"Fernando Gonzalez-Ortiz, Thomas K Karikari, Danielle Taylor-Te Vruchte, Dawn Shepherd, Bjørn-Eivind Kirsebom, Tormod Fladby, Frances Platt, Kaj Blennow","doi":"10.1093/braincomms/fcae375","DOIUrl":null,"url":null,"abstract":"<p><p>Niemann-Pick disease type C and Alzheimer's disease are distinct neurodegenerative disorders that share the presence of neurofibrillary tangle pathology. In this multicentre study, we measured plasma phosphorylated-tau217 in controls (<i>n</i> = 60), Niemann-Pick disease type C (<i>n</i> = 71) and Alzheimer's disease (<i>n</i> = 30 positive for amyloid and negative for tau in CSF [A<sup>+</sup>T<sup>-</sup>] and <i>n</i> = 30 positive for both [A<sup>+</sup>T<sup>+</sup>]). Annual Severity Increment Score and Lysotracker measurements were evaluated in the Niemann-Pick 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-Pick disease type C compared with controls (2.52 ± 1.93 versus 1.02 ± 0.34 pg/mL, respectively, <i>P</i> < 0.001) and inversely correlated with age at disease onset (<i>R</i> = -0.54, <i>P</i> < 0.001). In the longitudinal analysis, plasma phosphorylated-tau217 was associated with disease progression determined by Annual Severity Increment Score (<i>R</i> = 0.48, <i>P</i> < 0.001) and lysosomal enlargement (<i>R</i> = 0.26, <i>P</i> = 0.004). We found no differences between A<sup>+</sup>T<sup>-</sup> Alzheimer's disease and Niemann-Pick disease type C (2.67 ± 1.18 versus 2.52 ± 1. 93 pg/mL, <i>P</i> = 0.31); however, A<sup>+</sup>T<sup>+</sup> Alzheimer's disease had significantly higher levels than Niemann-Pick disease type C (3.26 ± 1.36 versus 2.52 ± 1.93 pg/mL, <i>P</i> = 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-Pick disease type C.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535543/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain communications","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/braincomms/fcae375","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Niemann-Pick disease type C and Alzheimer's disease are distinct neurodegenerative disorders that share the presence of neurofibrillary tangle pathology. In this multicentre study, we measured plasma phosphorylated-tau217 in controls (n = 60), Niemann-Pick disease type C (n = 71) and Alzheimer's disease (n = 30 positive for amyloid and negative for tau in CSF [A+T-] and n = 30 positive for both [A+T+]). Annual Severity Increment Score and Lysotracker measurements were evaluated in the Niemann-Pick 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-Pick disease type C compared with controls (2.52 ± 1.93 versus 1.02 ± 0.34 pg/mL, respectively, P < 0.001) and inversely correlated with age at disease onset (R = -0.54, P < 0.001). In the longitudinal analysis, plasma phosphorylated-tau217 was associated with disease progression determined by Annual Severity Increment Score (R = 0.48, P < 0.001) and lysosomal enlargement (R = 0.26, P = 0.004). We found no differences between A+T- Alzheimer's disease and Niemann-Pick disease type C (2.67 ± 1.18 versus 2.52 ± 1. 93 pg/mL, P = 0.31); however, A+T+ Alzheimer's disease had significantly higher levels than Niemann-Pick disease type C (3.26 ± 1.36 versus 2.52 ± 1.93 pg/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-Pick disease type C.