BIOBRIEFPAPER
A 363 protein scan of blood and spinal fluid, replicated in 52,990 UK Biobank participants, names neurofilament light chain (NEFL) — backed by proteins tied to immune activation and metabolic stress — as the most robust early ALS signal yet.
A new peer-reviewed study profiles 363 proteins in the blood and cerebrospinal fluid of 198 ALS patients and 125 matched controls, then replicates the findings in 52,990 UK Biobank participants. The result, published in the European Journal of Neurology, names neurofilament light chain (NEFL) as the most robust candidate marker in both compartments.
ALS is still diagnosed largely after motor symptoms appear, by which point motor neurons have already been lost. A blood-based signal that flags risk earlier could shorten the diagnostic odyssey and accelerate clinical-trial enrollment. Of the 363 proteins tested, 125 tracked with at least one of case status, risk, survival, or functional decline; 21 tracked with three or more.
NEFL is the standout because it indexes axonal injury directly. The supporting proteins cluster around biology that fits the disease: TNFRSF12A and EDA2R (immune activation) and FABP4 (metabolic and extracellular-matrix remodeling). Most also stayed stable across the disease course, which is what researchers want from a monitoring marker rather than a progression rate.
In the UK Biobank replication — 298 ALS cases among 52,990 participants with more than 3,000 measured plasma proteins — a risk-prediction model reached an ROC-AUC of 0.72. That is better than chance and useful for trial enrichment, but it is a research-grade signal, not a clinical test.