Serum p-tau181 and p-tau217 levels in adolescents and adults with 5q spinal muscular atrophy.
7 affiliations
- 1Department of Neurology, University Medicine Halle, Halle (Saale), Germany.
- 2Department of Neurology, University of Ulm, Ulm, Germany.
- 3Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, Leuven, Belgium.
- 4Department of Neuropediatrics, Centre for Neuromuscular Disorders in Children, University Hospital Essen, Duisburg-Essen University, Essen, Germany.
- 5Heimer Institute for Muscle Research, BG University Hospital Bergmannsheil Bochum, Bochum, Germany.
- 6Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
- 7Department of Neurology, University Medicine Halle, Halle (Saale), Germany. [email protected].
Abstract
Background
Reliable blood biomarkers for longitudinal monitoring in adolescent and adult 5q spinal muscular atrophy (SMA) are lacking. Phosphorylated tau (p-tau) species are elevated in serum in amyotrophic lateral sclerosis (ALS), where they may reflect peripheral nerve and muscle pathology. We aimed to investigate serum p-tau181 and p-tau217 as longitudinal biomarkers in adolescent and adult SMA and assessed associations with clinical parameters.Methods
In this retrospective multi-centre study, we assessed serum p-tau181 and p-tau217 levels in adults with 5q SMA under treatment with nusinersen or risdiplam, comparing levels with Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and non-neurodegenerative disease controls. Associations with motor function, respiratory capacity, creatine kinase (CK), and neurofilament light chain (NfL) were assessed using linear mixed-effects models adjusted for age and sex.Results
Serum p-tau181 was higher in SMA than in disease controls (β = -0.48, 95%-CI -0.81 to -0.15), but lower than in ALS (β = 0.99, 95%-CI 0.58 to 1.39) and AD (β = 0.56, 95%-CI 0.11 to 1.00). P-tau181 declined from baseline to FUP2 (Δ median -1.80 pg/mL, IQR -5.90 to 2.10); p-tau217 showed no longitudinal change. P-tau181 and p-tau217 were positively associated with motor function, functional status, respiratory capacity, and CK, with no association with NfL. In exploratory analyses, higher baseline p-tau181 was associated with greater HFMSE decline (β = 1.79, 95%-CI 0.59 to 2.99).Conclusions
Serum p-tau181 and p-tau217 appear to reflect ongoing muscle turnover in adult SMA, declining as muscle mass decreases. Higher baseline p-tau181 was associated with subsequent functional deterioration, suggesting potential utility as a biomarker of active denervation and disease monitoring.
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BibTeX
@article{stapf2026serum,
title = {{Serum p-tau181 and p-tau217 levels in adolescents and adults with 5q spinal muscular atrophy.}},
author = {Caroline Deborah Stapf and Zeljko Uzelac and Louise Iterbeke and Arthur Guthknecht and Lorenzo Barba and David Strube and Anna Kölsch and Kathleen Kleeberg and Thomas Kendzierski and Andreas Roos and Petra Steinacker and Samir Abu-Rumeileh and Kristl G Claeys and Jochen Weishaupt and Alexander Mensch and Markus Otto},
journal = {Journal of neurology},
year = {2026},
month = oct,
doi = {10.1007/s00415-026-14194-1},
url = {https://europepmc.org/article/MED/42905162},
note = {CC BY},
}
RIS
TY - JOUR
TI - Serum p-tau181 and p-tau217 levels in adolescents and adults with 5q spinal muscular atrophy.
AU - Caroline Deborah Stapf
AU - Zeljko Uzelac
AU - Louise Iterbeke
AU - Arthur Guthknecht
AU - Lorenzo Barba
AU - David Strube
AU - Anna Kölsch
AU - Kathleen Kleeberg
AU - Thomas Kendzierski
AU - Andreas Roos
AU - Petra Steinacker
AU - Samir Abu-Rumeileh
AU - Kristl G Claeys
AU - Jochen Weishaupt
AU - Alexander Mensch
AU - Markus Otto
PY - 2026
DA - 2026/10/21
JO - Journal of neurology
DO - 10.1007/s00415-026-14194-1
UR - https://europepmc.org/article/MED/42905162
AB - Background Reliable blood biomarkers for longitudinal monitoring in adolescent and adult 5q spinal muscular atrophy (SMA) are lacking. Phosphorylated tau (p-tau) species are elevated in serum in amyotrophic lateral sclerosis (ALS), where they may reflect peripheral nerve and muscle pathology. We aimed to investigate serum p-tau181 and p-tau217 as longitudinal biomarkers in adolescent and adult SMA and assessed associations with clinical parameters.Methods In this retrospective multi-centre study, we assessed serum p-tau181 and p-tau217 levels in adults with 5q SMA under treatment with nusinersen or risdiplam, comparing levels with Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and non-neurodegenerative disease controls. Associations with motor function, respiratory capacity, creatine kinase (CK), and neurofilament light chain (NfL) were assessed using linear mixed-effects models adjusted for age and sex.Results Serum p-tau181 was higher in SMA than in disease controls (β = -0.48, 95%-CI -0.81 to -0.15), but lower than in ALS (β = 0.99, 95%-CI 0.58 to 1.39) and AD (β = 0.56, 95%-CI 0.11 to 1.00). P-tau181 declined from baseline to FUP2 (Δ median -1.80 pg/mL, IQR -5.90 to 2.10); p-tau217 showed no longitudinal change. P-tau181 and p-tau217 were positively associated with motor function, functional status, respiratory capacity, and CK, with no association with NfL. In exploratory analyses, higher baseline p-tau181 was associated with greater HFMSE decline (β = 1.79, 95%-CI 0.59 to 2.99).Conclusions Serum p-tau181 and p-tau217 appear to reflect ongoing muscle turnover in adult SMA, declining as muscle mass decreases. Higher baseline p-tau181 was associated with subsequent functional deterioration, suggesting potential utility as a biomarker of active denervation and disease monitoring.
SN - 0340-5354
SN - 1432-1459
ER -