Plasma phosphorylated-tau217 is increased in Niemann-Pick disease type C.

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.
Competing Interests: K.B. has served as a consultant and at advisory boards for Acumen, ALZPath, BioArctic, Biogen, Eisai, Lilly, Moleac Pte Ltd, Novartis, Ono Pharma, Prothena, Roche Diagnostics and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; and has given lectures, produced educational materials and participated in educational programmes for AC Immune, Biogen, BioArctic, Celdara Medical, Eisai and Roche Diagnostics. K.B. is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. B.-E.K. has served as a consultant for Biogen. The other authors declare no competing interest.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)