Abdelhak A, Cerono G, Sheikhzadeh F, Harroud A, Ning K, Zamecnik CR, Sowa GM, Boscardin J, Cordano C, Tubati A, Fouassier C, Chow ED, Gomez R, Santaniello A, Zorn KC, Hollenbach JA, Oksenberg JR, Cree BAC, Hauser SL, Chan JR, Baranzini SE, Wallin MT, Wilson MR, Green AJ. Myelin injury precedes axonal injury and symptomatic onset in multiple sclerosis. Nat Med. 2025 Oct 20. doi: 10.1038/s41591-025-04014-w.
The timing of the biological onset of multiple sclerosis (MS) is unclear. We used high-throughput discovery proteomics and samples from presymptomatic patients with MS and matched healthy controls to define the biological neurological onset and characterize the mechanisms involved. Remarkably, evidence of myelin injury was seen ~7 years before the symptomatic onset and preceded evidence of axonal injury by ~1 year. By contrast, astrocyte involvement became evident only at clinical onset. Numerous changes in the serum proteome indicate the involvement of interleukin 3 (Immune growth and differentiation factor) and nuclear factor kappa B pathways (Immune activation) during the presymptomatic stage. Furthermore, people with MS with a previously reported distinct autoantibody signature showed increased immune cell activity compared to those without… Our findings can help understand the pathophysiology of MS as well as the cascade of central nervous system injury and might facilitate early detection of MS in high-risk people.
Source: multiple-sclerosis-research.org