Aging in multiple sclerosis alters the cerebrospinal fluid proteome, with inflammatory markers declining in older patients, according to a recent study.

The study investigated the influence of aging on the cerebrospinal fluid (CSF) proteome in multiple sclerosis (MS). Using targeted proteomics, researchers analyzed CSF from treatment-naïve patients in a discovery cohort of 88 participants (30 relapsing-remitting MS [RRMS], 30 primary progressive MS [PPMS], 8 neuroborreliosis, and 20 neurologic controls), with findings validated in a separate cohort of 28 participants (20 MS, 8 controls).

Among 2,500 proteins assessed, researchers identified 42 proteins with higher abundance and 5 with lower abundance in MS patients compared to controls. Key markers of B-cell activation and immune response, including TNFRSF13B and IL5RA, showed higher levels in MS. Notably, NEFL was the only serum protein that differed between MS and control groups, highlighting the limited utility of serum analysis compared to CSF.

While minimal differences were found between RRMS and PPMS proteomes, age significantly impacted the MS CSF profile. No significant differences emerged using an age cutoff of 40 years, but distinct changes appeared in patients over 50. In this older group, most inflammatory markers were less abundant, while proteins associated with biological aging, such as GDF15 and SORT1, became more prominent. This age-related shift may explain reduced immunotherapy efficacy in older patients.

The study, published in Neurology: Neuroimmunology & Neuroinflammation, also identified novel biomarkers, including LY9 and JCHAIN, and potential therapeutic targets such as SLAMF7 and BCMA, which are already approved for other indications. These results demonstrate the impact of aging on MS pathophysiology and underscore the importance of age consideration in treatment planning.

Full disclosures can be found in the published study.