Cerebrospinal Tau levels as a predictor of early disability in multiple sclerosis

Abstract

Introduction: Axonal loss is an important feature of Multiple Sclerosis (MS), being strongly related to irreversible disability accumulation. Nonetheless, the exact mechanisms underlying axonal loss remain unclear. Cerebrospinal fluid (CSF) levels of Tau and Beta-amyloid (Abeta) currently represent diagnostic biomarkers in other neurodegenerative diseases. In MS, studies on CSF Tau and Abeta provided preliminary informations on disease prognosis, but results have not yet been replicated.

Methods: We investigated whether CSF Tau and Abeta levels could predict early disability accumulation in MS patients. 100 patients underwent CSF analysis during their diagnostic work-up. Demographic, clinical, radiological features and CSF were collected at baseline. MS severity score (MSSS) and age-related MSSS (ARMSS) were calculated at last follow-up. We performed Mann-Whitney test, Spearman's coefficient, and multiple regression analysis for significant predictors of disability based on CSF Abeta and Tau levels, gender, age at diagnosis and MRI characteristics at baseline.

Results: Baseline CSF Tau levels moderately correlated with MSSS (r=0.372 p=0.0001) and weakly with ARMSS (r=0.237 p=0.0176) after a mean two years follow-up. Predictors of early disability evaluated with MSSS and ARMSS were CSF Tau (Beta:0.258 p=0.009 and Beta:0.252 p=0.01) and spinal cord involvement (Beta:0.196 p=0.029 and Beta:0.240 p=0.008); as well as age at MS diagnosis (Beta:0.286 p=0.001) for MSSS, and high brain lesion load (Beta:0.207 p=0.02) for ARMSS.

Conclusion: CSF Tau levels at diagnosis possibly has a predictive value along with MRI features and age at diagnosis. We hypothesize that Tau levels may express chronic axonal damage, possibly contributing to early MS disability.

Keywords: Biomarker; Multiple sclerosis; Neurodegeneration; Prognosis; Tau.