Cerebrospinal Fluid TAR DNA-Binding Protein 43 Combined with Tau Proteins as a Candidate Biomarker for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Spectrum Disorders

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are nowadays recognized as spectrum disorders with a molecular link, the TAR DNA-binding protein 43 (TDP-43), rendering it a surrogate biomarker for these disorders. Methods: We measured cerebrospinal fluid (CSF) levels of TDP-43, beta-amyloid peptide with 42 amino acids (A beta(42)), total tau protein (tau(T)), and tau protein phosphorylated at threonine 181 (tau(P)-181) in 32 patients with ALS, 51 patients with FTD, and 17 healthy controls. Double-sandwich commercial enzyme-linked immunosorbent assays were used for measurements. Results: Both ALS and FTD patients presented with higher TDP-43 and tau(T) levels compared to the control group. The combination of biomarkers in the form of the TDP-43 x tau(T) / tau(P)-181 formula achieved the best discrimination between ALS or FTD and controls, with sensitivities and specificities > 0.8. Conclusion: Combined analysis of TDP-43, tau(T), and tau(P)-181 in CSF may be useful for the antemortem diagnosis of ALS and FTD. (C) 2017 S. Karger AG, Basel