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

<b><i>Background:</i></b> 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. <b><i>Methods:</i></b> We measured cerebrospinal fluid (CSF) levels of TDP-43, beta-amyloid peptide with 42 amino acids (Aβ₄₂), total tau protein (τ_T), and tau protein phosphorylated at threonine 181 (τ_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. <b><i>Results:</i></b> Both ALS and FTD patients presented with higher TDP-43 and τ_T levels compared to the control group. The combination of biomarkers in the form of the TDP-43 × τ_T / τ_P-181 formula achieved the best discrimination between ALS or FTD and controls, with sensitivities and specificities >0.8. <b><i>Conclusion:</i></b> Combined analysis of TDP-43, τ_T, and τ_P-181 in CSF may be useful for the antemortem diagnosis of ALS and FTD.