Summary: Researchers identified a distinct cluster of blood proteins that alter in individuals who later develop multiple sclerosis (MS). The research leverages genetic statistical modeling and biobank tracking to isolate these biological markers, which manifest in the bloodstream up to a decade before a clinical diagnosis is made.
This landmark discovery opens the door to a preventative, proactive screening model, akin to checking cholesterol levels for cardiovascular disease, enabling clinicians to identify high-risk individuals and initiate protective interventions before permanent neurological damage occurs.
Key Facts
- The Prevention Paradigm: Within neurodegenerative care, prevention represents the most effective strategy, as established brain tissue damage is incredibly difficult or impossible to repair. Catching MS early allows clinicians to delay or altogether prevent its worst debilitating effects; however, modern diagnoses are frequently delayed until the disease is well underway and the window for early intervention has closed.
- The Proteomic Screen: To unearth early warning signals, researchers screened more than 2,500 blood proteins utilizing a specialized genetic statistical framework called Mendelian Randomization. The audit revealed that 39 specific proteins were directly linked to MS risk, with the vast majority cluster within the signaling pathways immune cells use to communicate.
- Deep Time Biobank Verification: To evaluate whether these molecules functioned as active early warning signs, the team utilized data from the UK Biobank, tracking the health trajectories of individuals who provided blood samples between 2006 and 2010. By examining a cohort of 124 individuals who later developed MS, scientists looked back at blood samples drawn an average of six years—and in some cases over ten years—prior to their clinical diagnosis.
- The Predictive Octet: The retrospective audit confirmed that eight distinct proteins were already significantly altered in the blood of individuals destined to develop MS.
- The Dual-Action Marker: Among the eight mapped proteins, a molecule designated as DKKL1 emerged as an elite marker. Elevated levels of DKKL1 were explicitly linked to both a significantly lower overall risk of developing MS and a markedly milder, less debilitating disease trajectory in individuals who did, making it an invaluable tool for both risk screening and patient prognosis.
- Validation and Scaling: Led by neurologist Dr. Adil Harroud, the research team plans to validate this predictive proteomic signature across larger patient cohorts. The ultimate goal is to integrate these markers with existing diagnostic tools to construct a universal, non-invasive blood screening test for clinical use.
Source: McGill University
A new study has revealed a group of blood proteins, that are altered in people who go on to develop multiple sclerosis (MS), in some cases more than a decade before diagnosis. The findings offer hope that a simple blood test could one day identify people at high risk of MS in time to act before damage occurs.
The best cure for neurological diseases like MS is prevention. Brain damage already done is difficult or impossible to repair, but if MS is caught early, the worst of its debilitating effects can often be prevented. Unfortunately, in many cases, diagnosis comes only after the disease is well underway and the window for early intervention has passed.
A team of scientists led by Dr. Adil Harroud, a neurologist and researcher at The Neuro (Montreal Neurological Institute-Hospital) of McGill University, sought ways to detect signs of future MS in patients’ blood years before they were diagnosed. They focused on proteins, the molecules that carry out most of the body’s functions.
Out of more than 2,500 blood proteins screened using a statistical technique known as Mendelian Randomization, the team found that 39 were linked to MS risk, most of them in the signalling pathways immune cells use to communicate.
To know whether these proteins could serve as an early warning, they turned to UK Biobank, a comprehensive biomedical dataset which collected blood samples from half a million UK volunteers between 2006-2010 and has tracked their health since. Among them, 124 went on to develop MS, allowing the researchers to look back at samples taken on average six years before diagnosis, and in some cases more than a decade earlier.
In those samples, the scientists found that eight proteins were already altered in people who would later be diagnosed with MS. One of them, DKKL1, was linked to both a lower risk of developing MS and a milder course of disease in those who did, making it a candidate marker for both risk and prognosis. The logic resembles cholesterol screening for heart disease, where blood levels can flag risk years before a heart attack and give doctors time to intervene.
“In MS, we now know that intervening early can delay or even prevent symptoms altogether,” says Dr. Harroud. “What we lack is a way to identify the right people in time. These blood markers point toward a way to do that, and to act before damage is done.”
The team plans to validate the findings in larger cohorts and to test whether these markers, combined with other tools, can be developed into screening tests.
The study was published in the journal Annals of Neurology on May 22, 2026.
Funding: It was supported with funds from Fonds de Recherche du Québec Santé, the Bougie Family Young Investigator Award, the Brain Canada Foundation, and the Canada Brain Research Fund. The UK Biobank application number for this project is 45551.
Key Questions Answered:
A: Because when it comes to diseases like multiple sclerosis, the best cure is stopping it before it starts. Brain damage that has already occurred is often impossible for the body to fix. Catching the disease a decade early allows doctors to step in during a hidden window of opportunity, using early treatments to preserve brain tissue and delay or completely prevent the onset of disabling symptoms.
A: The study highlighted a unique protein called DKKL1 that acts as a dual-action diagnostic compass. When researchers looked back at blood samples taken years before diagnosis, they found that altered levels of DKKL1 directly correlated with a lower risk of developing MS. Furthermore, if the person did end up developing the condition, DKKL1 predicted a much milder, less severe course of the illness, serving as a powerful tool for both early risk detection and long-term prognosis.
A: It matches the exact logic of a standard cholesterol check. Doctors don’t wait for a patient to suffer a massive heart attack before they start measuring cholesterol; they screen the blood years in advance to flag high risk and change the patient’s treatment plan early. This discovery aims to bring that exact same preventative mindset to neurology, using a simple blood test to stop neurological damage before it ever hits the brain.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this multiple sclerosis research news
Author: Shawn Hayward
Source: McGill University
Contact: Shawn Hayward – McGill University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Genetic-Proteomic Integration Identifies Predictive Plasma Proteins for Multiple Sclerosi” by Yuan Ding MSc, Dylan Hamitouche, Simon Thebault MD, PhD, Patrick Kearns MBChB, MPH, Ahmed Abdelhak MD, PhD, Adil Harroud MD. Annals of Neurology
DOI:10.1002/ana.78256
Abstract
Genetic-Proteomic Integration Identifies Predictive Plasma Proteins for Multiple Sclerosi
Objective
Multiple sclerosis (MS) develops after a prolonged preclinical phase. Identifying circulating biomarkers that capture this early biology can improve risk stratification and guide intervention. We aimed to identify plasma proteins driving MS susceptibility using large-scale proteogenomic integration and to evaluate their prediagnostic predictive value and effects on severity.
Methods
We used cis-acting protein quantitative trait loci (pQTL) for 2,545 plasma proteins (n = 80,824). Predicted protein levels were tested for association with MS risk in 14,802 cases and 26,703 controls using Mendelian randomization and colocalization. Splicing annotations were integrated to interpret platform-specific discrepancies. We validated candidates as predictors of incident MS in prediagnostic United Kingdom Biobank samples (124 cases, 52,515 controls; median 5.9 years prediagnosis) and assessed associations with disease severity (n = 12,584).
Results
We identified 39 proteins associated with MS risk. Most formed a densely connected network enriched in immune regulatory pathways, B- and T-cell costimulation, cytokine signaling, and Epstein–Barr virus-related pathways. Transcriptomic enrichment was strongest in B-cell subsets. Splicing data suggested that discordances between proteomic platforms reflect distinct proteoforms.
Among 28 genetically implicated proteins measured in prediagnostic samples, 8 were associated with time to MS diagnosis, demonstrating enrichment beyond chance expectation (pbinom = 4.92 × 10−5). DKKL1 showed concordant protective associations across risk, incidence, and severity. Integrating pQTLs improved fine-mapping resolution at colocalized loci by >10-fold and nominated 13 putative novel risk loci.
Interpretation
This integrated genetic-proteomic framework identifies causal proteins, refines risk loci, and supports the development of early predictive biomarkers with translational potential. These findings support genetically anchored biomarkers for preclinical disease detection and intervention.
