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Impact of Plasma p-tau181 on Cognition, Motor Phenotypes, and Disease Course in ALS.

Annals of clinical and translational neurology

Authors: Elisabeth Kasper, Annaliis Lehto, Nina Nordmann, Oliver Peters, Julian Hellmann, Josef Priller, Eike Jakob Spruth, Gabor C Petzold, Ina Vogt, Patrick Weydt, Sarah Bernsen, Elisabeth Dinter, Björn Falkenburger, René Günther, Emrah Düzel, Wenzel Glanz, Matthis Synofzik, Lukas Beichert, Annika Spottke, Michael Wagner, Frederic Brosseron, Matthias C Schmid, Anja Schneider, Stefan Teipel, Johannes Prudlo, Andreas Hermann

Phosphorylated tau181 (p-tau181), an Alzheimer's disease biomarker, was recently evaluated in amyotrophic lateral sclerosis (ALS). We investigated plasma p-tau181 in 202 ALS/ALS-FTD patients and 94 healthy controls, assessing cognitive performance, motor function, and longitudinal dynamics. Plasma p-tau181 and NfL were significantly elevated in ALS, with p-tau181 increasing over 1 year while NfL remained stable. Neither marker correlated with cognitive performance, and only NfL was associated with disease severity and progression. Plasma p-tau181 was higher in patients with predominant lower motor neuron involvement. The results indicate that p-tau181 reflects peripheral processes in ALS, providing a complementary, mechanistically distinct biomarker from NfL.

© 2026 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

PMID: 42080410

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