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

Abstract

Background: 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 (Aβ42), total tau protein (τT), and tau protein phosphorylated at threonine 181 (τP-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 τT levels compared to the control group. The combination of biomarkers in the form of the TDP-43 × τT / τP-181 formula achieved the best discrimination between ALS or FTD and controls, with sensitivities and specificities >0.8.

Conclusion: Combined analysis of TDP-43, τT, and τP-181 in CSF may be useful for the antemortem diagnosis of ALS and FTD.

Keywords: Amyotrophic lateral sclerosis; Beta-amyloid; Frontotemporal dementia; TAR DNA-binding protein 43; Tau protein.