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.