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A glial oxidative signature predicts disability in primary progressive multiple sclerosis and is associated with long-term cognitive decline
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A glial oxidative signature predicts disability in primary progressive multiple sclerosis and is associated with long-term cognitive decline
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Journal Article
A glial oxidative signature predicts disability in primary progressive multiple sclerosis and is associated with long-term cognitive decline
2026
Overview
Progressive multiple sclerosis (MS) involves heterogeneous mechanisms, and primary progressive MS without inflammatory activity (PPMS-NA) is poorly understood.
To characterize the immune-oxidative profile of PPMS-NA and assess plasma IL-6, IL-8, IFNα2, and cerebrospinal fluid (CSF) reactive oxygen species (ROS) as predictors of disability and cognitive decline.
We conducted a multicenter longitudinal study with two cohorts. Cohort 1 included participants across MS phenotypes (n = 146 baseline; n = 36 follow-up) and other neurological disorders, measuring plasma cytokines and CSF ROS. Cohort 2 included 40 people with MS, followed for 10 years to assess associations with cognition. Outcomes were analyzed with multivariate models.
PPMS-NA showed reduced IL-6 and IFNα2 but elevated CSF ROS versus RRMS and OND, reflecting low systemic inflammation and central oxidative stress. IL-8 increased, predicting disability and 10-year processing speed decline. IL-6 had time- and domain-specific effects: initially linked to attention, later inversely with visuospatial and working memory. CSF ROS correlated with atrophy, supporting oxidative stress as neurodegeneration driver.
PPMS-NA is a progressive MS subtype driven by oxidative and glial processes. IL-8 and CSF ROS are biomarkers for early stratification, and IL-6 relates to cognition, supporting therapies targeting oxidative stress and glia.
Publisher
Frontiers Media SA,Frontiers Media S.A
Subject
/ Atrophy
/ Biomarkers - cerebrospinal fluid
/ Cognitive Dysfunction - diagnosis
/ Cognitive Dysfunction - etiology
/ Cognitive Dysfunction - metabolism
/ Disease
/ Female
/ Females
/ Humans
/ Male
/ Multiple Sclerosis, Chronic Progressive - cerebrospinal fluid
/ Multiple Sclerosis, Chronic Progressive - diagnosis
/ Multiple Sclerosis, Chronic Progressive - immunology
/ Multiple Sclerosis, Chronic Progressive - metabolism
/ Multiple Sclerosis, Chronic Progressive - psychology
/ Reactive Oxygen Species - cerebrospinal fluid
/ Reactive Oxygen Species - metabolism
/ Software
