Plasma tau and phosphorylated tau at T181 are altered in amyotrophic lateral sclerosis

There is an unmet need for reliable biomarkers for amyotrophic lateral sclerosis (ALS). Recent studies have demonstrated that the levels of the microtubule-associated protein tau, are altered in plasma and cerebrospinal fluid (CSF) from people with ALS. Our previous findings demonstrated that while the ratio between tau and phosphorylated tau at T181 (pTau-T181) is decreased, increases in CSF tau correlated with faster disease progression in people with ALS. Here, we measured tau and pTau-T181 in plasma samples from participants with ALS and healthy controls (HC) using two methods (Quanterix Simoa and Meso Scale Discovery, MSD). Using both assays, there was an increase in pTau-T181 levels and in the pTau-T181:tau ratio in ALS compared to HC andlarger increases in pTau-T181 and pTau-T181:tau ratio at baseline correlated with faster ALS progression. Plasma total tau levels were increased in ALS compared to HC on the MSD assay and decreased on Quanterix Simoa assay. Collectively, our results suggest that plasma pTau-T181 levels are increased in ALS. Future studies should aim to clarify its role as a diagnostic or prognostic biomarker for ALS.