Cerebrospinal fluid (CSF) tau and beta-amyloid (Aβ) proteins are among the biomarkers currently applied in other neurodegenerative diseases than MS. Partly due to conflicting results, not a single biomarker of axonal damage in MS is routinely used in clinical practice. Now, a new prospective study shows that Aβ and especially CSF tau can help identify early disability and unfavorable prognosis in MS patients, independent of age.

An Italian group set out to evaluate if CSF tau and Aβ protein concentrations (collected at diagnosis) could predict early MS disability, and if there was a correlation between CSF tau and Aβ protein with other radiological prognostic markers collected at baseline [1].

The researchers used a commercial enzyme-linked immunosorbent assay to measure CSF tau and Aβ levels. They collected demographic, clinical, and radiological data at baseline and at the most recent clinical follow-up. Early disability was measured using the MS severity score (MSSS) and the MSSS age-related score (ARMSS) at the most recent follow-up. Radiological prognostic markers were global T2 white matter lesion load and spinal cord lesions. A total of 109 MS patients (82 with relapsing-remitting MS), were followed for a mean period of 4 years.

Patients with higher CSF tau levels at baseline had higher MSSS (R=0.336; P=0.0003) and ARMSS (R=0.3088; P=0.001) at follow-up. There were no correlations between CSF Aβ and markers of early disability thus far. In patients with higher T2 white matter lesion load, there was a trend towards higher tau levels and lower Aβ levels. Patients with spinal cord involvement also showed a trend towards higher tau. There was a significant correlation between CSF tau and early disability, both when measured with MSSS or ARMSS.

These results led to the conclusion that CSF tau and Aβ may correlate with negative prognostic factors at diagnosis, particularly with high lesion load and spinal cord involvement. Tau may have a predictive role in identifying early disability in MS patients. This role remains to be determined. This is the first study to report a correlation between CSF tau and MSSS as well as ARMSS. To confirm these results, longer follow-up, a larger population, and extended analysis of radiological data are needed. Several open questions remain: which CSF cut-off values should be deployed in MS? What is the relationship with advanced imaging evaluation, and with other axonal damage biomarkers?

1. Virgilio E, et al. MSVIRTUAL2020, Abstract PS03.02.