Key result
Adult spinal muscular atrophy is linked to elevated circulating pTau-262, suggesting potential as a biomarker.
Why the study?
Alterations in circulating Tau and phosphorylated Tau profiles in pediatric and adult patients with spinal muscular atrophy were not well characterized.
Are circulating Tau and phosphorylated Tau profiles altered in pediatric and adult patients with spinal muscular atrophy?
Observational (n=109)
Yes
Are circulating Tau and phosphorylated Tau profiles altered in pediatric and adult patients with spinal muscular atrophy?
Circulating pTau-262 may serve as a disease-relevant biomarker in adult SMA, while transient Tau elevations after gene therapy in pediatric patients suggest acute neuronal stress.
pTau-262 elevation may support biomarker exploration in adult SMA; hypothesis-generating and requires prospective validation before clinical use.
Objective: To determine alterations in circulating Tau and phosphorylated Tau (pTau) profiles in pediatric and adult patients with spinal muscular atrophy (SMA). Methods: Circulating total Tau, pTau-181, pTau-217, pTau-262, and pTau-396 concentrations were measured across three cohorts: 1) adults including healthy controls, SMA patients, and ALS patients; 2) pediatric SMA patients and age-matched controls; and 3) pediatric SMA patients treated with onasemnogene abeparvovec. Results: Distinct alterations in circulating Tau species were detected in adult SMA and ALS. Among all measurements, pTau-262 emerged as the only species specifically elevated in adult SMA, while total Tau levels were comparable between adult SMA and controls but significantly increased in ALS. Tau alterations were not consistently observed in pediatric SMA, although a small subset showed elevated levels, underscoring the value of individualized biomarker monitoring upon diagnosis. In gene-therapy-treated infants, Tau levels increased transiently several weeks after onasemnogene abeparvovec injection, paralleling previously described neurofilament kinetics and suggesting acute, treatment-associated neuronal stress. Conclusions: Circulating Tau, particularly pTau-262, may serve as a disease-relevant biomarker in adult SMA, while pediatric profiles appear more heterogeneous. Transient Tau elevations after gene therapy may reflect acute neuronal vulnerability and warrant further investigation.
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Ha et al. (2025) conducted an observational in Spinal Muscular Atrophy (SMA) (n=109). Spinal Muscular Atrophy vs. Healthy controls and ALS patients was evaluated on Circulating pTau-262 concentration (p=<0.05). Circulating pTau-262 levels were specifically elevated in adult patients with spinal muscular atrophy compared to healthy controls, suggesting its potential as a disease-relevant biomarker.
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