# Serum p-tau181 and p-tau217 levels in adolescents and adults with 5q spinal muscular atrophy

Article · Stapf CD, Uzelac Z, Iterbeke L, Guthknecht A, Barba L, Strube D, Kölsch A, Kleeberg K, Kendzierski T, Roos A, Steinacker P, Abu-Rumeileh S, Claeys KG, Weishaupt J, Mensch A, Otto M

- Archive id: doi:10.1007/s00415-026-14194-1
- Published: 2026-10-21
- Venue: Journal of neurology
- DOI: https://doi.org/10.1007/s00415-026-14194-1
- PMID: 42905162
- PMCID: PMC13687299
- Citations: 0
- Source URL: https://doi.org/10.1007/s00415-026-14194-1
- PDF: https://europepmc.org/articles/PMC13687299/pdf
- Provenance: europepmc

## 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.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Alzheimer's, Parkinson's & Neurodegeneration](https://space-kitty.com/topics/neurodegeneration)

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