What is it about?
ALS may begin changing the body years before symptoms appear. We analyzed repeated blood samples from people at genetic risk of ALS and identified protein changes that precede symptom onset. A 19-protein panel helped predict whether and when clinically manifest ALS would develop.
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Why is it important?
One of the major barriers to preventing ALS is that we currently cannot reliably determine when an apparently healthy person at genetic risk is approaching disease onset. Our study shows that changes in multiple blood proteins can be detected before symptoms emerge and that combining these biomarkers provides more information about the timing of ALS onset than relying on a single biomarker such as neurofilament light (NfL). With further validation, such biomarkers could help identify people who are approaching the clinical phase of ALS, improve participant selection and timing in disease-prevention trials, and ultimately support interventions at an earlier stage of disease.
Perspectives
For people who carry ALS-associated genetic variants, an important unanswered question is not only whether they may develop ALS, but when. We wanted to determine whether the transition from a clinically unaffected state to symptomatic ALS leaves a measurable molecular signature in blood. By analyzing longitudinal plasma samples, we found that ALS-associated biological changes are not confined to the period immediately before diagnosis: multiple proteins follow distinct trajectories months to years before symptoms appear. A particularly encouraging finding was that a multi-protein signature provided substantially more information about the timing of phenoconversion than a single biomarker alone. This supports the view that pre-symptomatic ALS is a dynamic biological process that may be better captured by combinations of biomarkers. The next step is to validate these findings in larger and more diverse cohorts and to determine whether a practical biomarker panel can be developed for use in prevention trials and, eventually, clinical risk assessment.
Ximing Ran
Emory University
Read the Original
This page is a summary of: Longitudinal plasma proteomics predict phenoconversion to clinically manifest ALS, Nature Medicine, July 2026, Springer Science + Business Media,
DOI: 10.1038/s41591-026-04528-x.
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