The research team analyzed blood plasma from 632 ALS patients and 160 healthy control participants using high-sensitivity technology. By examining the levels of 10 specific proteins together, the investigators separated the two groups with a balanced accuracy of 98.3 percent.
NULISA Technology Measures Microscopic Protein Levels in Blood Plasma
The scientific team utilized an ultra-sensitive method known as NULISA, or nucleic acid-linked immunosorbent sandwich assay, to measure minute quantities of circulating proteins simultaneously. Emory’s Neurodegenerative Disease Research Center and ALS Center investigators initially screened more than 300 neurological and inflammatory proteins from the participant blood plasmas.
Computer-driven analytical models narrowed the candidates down to 12 proteins before finalizing the selection at 10. The panel includes four previously recognized ALS biomarkers—neurofilaments NFL and NEFH, phosphorylated tau pTau-181, and VEGFA—alongside six proteins not previously linked to ALS in blood diagnostics: CALCA, NRGN, PTX3, TREM1, FOLR1, and LAMP3.
Validation Cohort Confirms 98.3 Percent Balanced Accuracy
In a separate validation cohort consisting of 144 ALS patients and 37 control participants, the 10-protein panel achieved a balanced accuracy of 98.3 percent with an area under the curve of 0.992. That performance significantly surpassed the 89.9 percent accuracy and 0.916 AUC generated by testing for the single neurofilament light chain biomarker alone.
Conventional NFL tests often register elevated readings in individuals with alternative neurodegenerative conditions or systemic illnesses, which limits their diagnostic specificity. The inclusion of the FOLR1 protein specifically helped correctly categorize non-ALS patients who displayed high NFL levels, reducing false-positive results from legacy screening methods.
Diagnostic Implications for Early-Stage Patients
The protein panel also identified ALS cases among patients with relatively low initial disability levels whose conditions proved difficult to diagnose through single-marker analysis alone.
The newly identified protein combination remains strictly in the research phase and is not yet cleared as a clinical diagnostic test. Investigators plan to conduct further validation studies across larger and more diverse patient cohorts.
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