Tau Levels May Predict Early Disability, Worse Prognosis in MS

Author(s):

Data show that higher CSF tau levels at diagnosis correlated with worse disability independent of age, though no such associations were identified with amyloid-beta.

Eleonora Virgilio, MD

The results of an evaluation of cerebrospinal fluid (CSF) tau and amyloid-beta proteins suggest that these CSF biomarkers, particularly tau, might serve as predictive markers of early disability and worsened prognosis in patients with multiple sclerosis (MS).

All told, the markers of neurodegeneration were assessed in 109 patients, 82 of whom had relapsing-remitting MS. Those with higher CSF tau levels at the time of diagnosis developed higher disability as measured by MS severity score (MSSS) and MSSS age-related score (ARMSS), independent of age. No associations were found for amyloid-beta.

The data were presented by Eleonora Virgilio, MD, doctoral student, University of Piemonte Orientale, at MS Virtual 2020, the 8th joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020. “To our knowledge, no other studies report a correlation of CSF Tau with both MSSS and ARMSS. Longer follow-up, larger population, and extended analysis of radiological data are needed, to confirm a predictive and prognostic role of our biomarkers both at baseline and follow up,” they wrote.

The mean follow-up for the study was 4 years (standard deviation [SD], 5), with the mean CSF values of tau being 128.5 pg/mL (±69) and of amyloid-beta being 557.7 pg/mL (±258.6). About two-thirds (62.4%) of the cohort was female, the mean age at onset of disease was 36.3 years, and the mean diagnosis age was 38.7 years. Median Expanded Disability Scale Status (EDSS) score was 1.5.

The aforementioned group with higher tau values at disease onset predicted early disability withthe MSSS (β, 0.258; R2 0.24; 95% CI, 0.02–0.14; P = .009) and with ARMSS (β, 0.252; R2 0.22; 95% CI, 0.02–0.12; P = .001) in multiple regression analysis.

“We also found a trend of higher tau level and lower amyloid-beta levels with higher T2 white matter lesion load and spinal cord involvement, still statistically not significant,” Virgilio and colleagues wrote. Approximately half of the study cohort, 54.1%, reported high white matter lesion load, and similarly, just under half, 45.9%, reported spinal cord involvement. The proportion of patients with contrast-enhanced lesions was 25.7%.

CSF amyloid-beta and tau levels were determined with commercial enzyme-linked immunosorbent assay in newly diagnosed patients with MS. The group collected demographic, clinical, and radiological data at baseline and at the last clinical follow-up.

Neurofilament light chain (NfL) protein has dominated the conversation about MS-related biomarkers over the last few years, though a number of other projects have explored additional evidence of effective biomarkers. In early 2020, the results of one such study revealed that lowered levels of the total radical-trapping antioxidant parameter (TRAP), adiponectin, zinc, and soluble tumor necrosis factor (TNF)-α receptor (sTNFR) 2 are associated with the disease activity of MS. Notably, these antioxidants were deemed more important biomarkers than TNF-α signaling and nitro-oxidative biomarkers.²

Conducted by Edna Maria Vissoci Reiche, MD, and colleagues, the study included 174 patients with MS, including 5 with clinically isolated syndrome (CIS), 144 with relapse-remitting MS (RRMS), and 25 with progressive clinical forms of MS. In total, 5 of those patients had primary progressive MS (PPMS) and 20 had secondary progressive MS (SPMS).

The data revealed that patients with MS all had lowered levels of TRAP, zinc, adiponectin, and SH groups (all P = .001). Patients with this combination of antioxidants were correctly classified in 95.5% of cases, with a sensitivity of 95.7% and specificity of 95.1%. Investigators noted a .986 (+0.005) area under the curve (AUC)/receiver operating characteristic (ROC) curve based on these 4 antioxidants. Additionally, those with that combination of antioxidants displayed higher levels of AOPP (P = .041), NOx (P = .046), TNF-A (P <.001), and sTNFR2 (P <.001) than controls.

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REFERENCES
1. Virgilio E, Vecchio D, Crespi I, et al. Biomarkers of neurodegeneration, in particular Tau protein, may predict early disability in Multiple Sclerosis patients. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract PS03.02.
2. Mezzaroba L, Simao AC, Oliveira SR, et al. Antioxidant and anti-inflammatory diagnostic biomarkers in multiple sclerosis: a machine learning study. Mol Neurobiol (2020).doi : 10.1007/s12035-019-01856-7.