Tau protein as a diagnostic and prognostic biomarker in amyotrophic lateral sclerosis

Abstract

BACKGROUND: To test the hypothesis that total tau (tTau), tau phosphorylated at threonine 181 (pTau) and the pTau/tTau ratio in the cerebrospinal fluid (CSF) are diagnostic and prognostic biomarkers of amyotrophic lateral sclerosis (ALS), we performed a retrospective observational study on a large cohort of ALS patients and controls.METHODS: We enrolled 196 ALS patients and 91 controls, including ALS-mimics and patients with non-neurodegenerative diseases. All patients underwent lumbar puncture for CSF analysis at the time of the diagnostic work-up or to first referral. We measured tTau and pTau levels in the CSF by chemiluminescence enzyme immunoassay (CLEIA).RESULTS: ALS patients showed significantly higher levels of CSF tTau and lower pTau/tTau ratio than controls (tTau: 245 vs 146 pg/mL; p<0.001; pTau/tTau ratio: 0.12 vs 0.18; p<0.001, respectively). No differences of pTau levels were detected. The analysis of the receiver operating characteristic (ROC) curve showed a good diagnostic accuracy of tTau and pTau/tTau ratio (tTau: AUC 0.685, 95%CI 0.616-0.754, p=0.039; pTau/tTau ratio: AUC 0.777, 95%CI 0.707-0.848, p<0.001). Among ALS patients, increased tTau levels were associated with the advanced age of onset, increased DeltaFS, rate of progression, and spinal onset. The multivariate analysis showed that in ALS patients, this biomarker was an independent negative predictor of overall survival.CONCLUSIONS: Our findings suggest that tTau and pTau/tTau ratio can be diagnostic biomarkers of ALS. Finally, CSF tTau level at diagnosis might play a relevant prognostic role in the disease.