Can Tau Predict Early MS Disability?

Tau predicted early disability and worse prognosis in multiple sclerosis (MS) patients independently of age, a longitudinal prospective study showed.

MS patients with higher cerebrospinal fluid (CSF) tau levels at diagnosis developed higher MS Severity Scores (MSSS) and Age-Related MS Severity Scores (ARMSS) over 4 years than those with lower tau levels, reported Eleonora Virgilio, MD, of University of Piemonte Orientale in Italy, at MSVirtual 2020, the joint ACTRIMS-ECTRIMS meeting. No significant relationship was seen for beta amyloid.

Neurodegeneration occurs early in MS, Virgilio noted. "Neurofilament light chain has been investigated as an axonal damage biomarker in MS, but it is not routinely used in clinical practice," she said. "On the other hand, CSF tau and beta amyloid proteins are currently used in other neurodegenerative diseases, like Alzheimer's disease."

"Although CSF levels of tau protein have not been directly compared with neurofilament in individuals with MS, this study suggests CSF tau as an alternative prognostic marker that predicts the development of higher disability in newly diagnosed patients," noted Benjamin Segal, MD, of The Ohio State University in Columbus, who wasn't involved with the research.

"The relationship was highly significant and it was independent of age," Segal told MedPage Today. "The investigators also found a trend of higher tau level and brain MRI lesion burden and spinal cord lesion. If these data are reproduced in larger studies, these data indicate that CSF tau might complement neurofilament in predicting the future clinical course."

Previous research has looked at both tau and beta amyloid in MS -- for differential diagnosis, disease progression, or to track particular characteristics like cognition -- with mixed results, Virgilio said.

In this study, Virgilio and colleagues enrolled 109 newly diagnosed MS patients, including 95 with relapsing-remitting MS, and followed them for an average of 4 years. CSF samples were collected at diagnosis (baseline). Global T2 white matter lesion load (with more than nine lesions considered high), presence of spinal cord lesions, and presence of gadolinium lesions were used as radiological baseline prognostic markers. Disability outcomes were determined by MSSS and ARMSS at last follow-up.

Nearly two-thirds (62.4%) of the sample was female. Mean onset age was 36.3, and mean diagnosis age was 38.7. Median Expanded Disability Scale Status (EDSS) score was 1.5. About half of the study population showed high white matter lesion load (54.1%) and spinal cord involvement (45.9%); the proportion with contrast-enhanced lesions was 25.7%. CSF tau values averaged 134.80 pg/ml and beta amyloid values averaged 623.27 pg/ml.

Tau predicted early disability with MSSS (β 0.258, R² 0.24, 95% CI 0.02-0.14, P=0.009) and with ARMSS (β 0.252, R² 0.22, 95% CI 0.02-0.12, P=0.01) in multiple regression analysis. A nonsignificant trend between higher tau and greater lesion load and spinal cord involvement also emerged. There were no significant relationships for beta amyloid.

"This is an interesting result, showing raised tau in the CSF of patients with MS," observed Gavin Giovannoni, MBBCh, PhD, of Queen Mary University of London, who wasn't involved with the study.

"It is unlikely to be specific to MS, but maybe an important prognostic marker," Giovannoni told MedPage Today. "Further longitudinal studies comparing tau with other markers, such as neurofilament light chain levels, will need to be done."

"To our knowledge, no previous study has used the Age-Related MS Severity Score to define a correlation between tau and early disability," Virgilio noted. The roles played by tau and beta amyloid in MS physiopathology remain to be determined, "but we suggest a role, in particular of tau protein, in neurodegeneration that merits more investigation," she said.

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