The findings, published in the international journal Nature Communications, offer a significant leap forward from existing single-marker blood tests.
Researchers Analyze Blood Proteins to Identify ALS Markers
The research team at Emory analyzed blood plasma samples from 632 ALS patients and 160 healthy control participants. Utilizing a high-sensitivity technology called NULISA, the investigators measured over 300 neurological and inflammatory proteins in the plasma samples.
Computer analysis initially narrowed the candidates down to 12 before researchers selected the final 10 proteins. This panel includes four established ALS blood markers—neurofilaments (NFL and NEFH), phosphorylated tau (pTau-181), and VEGFA—alongside six proteins previously unreported as ALS blood markers in this context: CALCA, NRGN, PTX3, TREM1, FOLR1, and LAMP3. In a separate validation cohort consisting of 144 ALS patients and 37 controls, this 10-protein combination achieved a balanced accuracy of 98.3% with an AUC of 0.992. That performance notably outstrips the 89.9% accuracy and 0.916 AUC of the standard neurofilament light chain single test.
| Test Method | Protein Markers | Balanced Accuracy | AUC Score |
|---|---|---|---|
| Standard Assay | NFL (Single Marker) | 89.9% | 0.916 |
| Emory Panel | 10-Protein Combination | 98.3% | 0.992 |
Addressing Limitations of Existing Diagnostics
Traditional neurofilament testing often presents limitations in specificity because NFL levels can rise across various neurodegenerative and systemic conditions. The inclusion of proteins such as FOLR1 within the new Emory panel specifically aids in correctly classifying non-ALS patients who exhibit high NFL levels, thereby cutting down on false positives.
The protein combination successfully identified ALS patients who presented with relatively low disability levels—cases that are traditionally difficult to diagnose and frequently missed by an NFL-only test.
Early Screening Eliminates Unnecessary Tests According to Researcher
Jonathan Han, a professor, director of the Emory ALS Center and co-corresponding author of the study, emphasized the toll that prolonged diagnostic pathways take on patients and their families. “The time it takes to receive an ALS diagnosis is very difficult for patients and their families,” Han noted, pointing out that an early screening tool helps eliminate unnecessary tests and connects patients to specialized care much faster.
Despite the high accuracy rates recorded in the validation group, the protein combination remains in the research phase and is not yet a clinically validated diagnostic test. The research team intends to carry out additional validation studies across larger and more diverse patient populations before clinical implementation.
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