Blood Test Detects Early Signs of ALS Years Before Symptoms Appear

The disease leads to muscle weakness, loss of mass, and ultimately respiratory failure. By 2040, experts estimate that nearly 400,000 people worldwide will be living with ALS. Diagnosis today relies on neurological evaluation and symptoms, with no definitive test available, leaving many patients diagnosed only after significant progression. Now, a new blood test has shown potential to detect ALS years before symptoms appear.

Researchers at Johns Hopkins University School of Medicine (Baltimore, MD, USA) and collaborators have identified a distinct blood-based protein signature predictive of ALS. Using a platform that measured nearly 3,000 proteins in samples from over 600 participants, the team applied machine learning to isolate markers linked to ALS. The result was a diagnostic model with more than 98% accuracy in distinguishing ALS from healthy individuals and other neurological diseases.

Their study, published Aug. 19 in Nature Medicine, analyzed samples from patients with ALS and from individuals who had donated blood years before developing the disease. It revealed protein changes related to skeletal muscle, nerve signaling, and energy metabolism up to a decade before symptoms appeared. The model was validated in multiple groups, including a 23,000-participant UK Biobank cohort, where samples from 110 individuals collected 10–15 years before diagnosis already showed the protein signature.

This discovery suggests ALS is not as rapid in onset as once believed, but rather develops silently over years. Detecting changes long before symptoms could transform diagnosis, enable earlier treatment, and improve clinical trial enrollment. Importantly, the signature was not driven by genetic mutations, meaning it may apply broadly to patients regardless of family history. The ability to differentiate ALS from conditions like Parkinson’s disease adds diagnostic clarity and reduces the risk of misdiagnosis.

Future research will focus on using the protein signature to monitor disease progression and assess treatment effectiveness. The data has been made publicly available to accelerate biomarker development, with researchers also exploring its potential application to other neurodegenerative diseases. The team plans to refine the test for use in clinical settings, aiming for widespread adoption to support earlier interventions.

“We see the light at the end of the tunnel here, and that target is an approved and available blood test for ALS,” said Alexander Pantelyat, M.D., associate professor of neurology at Johns Hopkins University School of Medicine. “With a test that allows for earlier detection of ALS, we have opportunities to enroll people in observational studies, and by extension, offer promising disease-modifying — and hopefully disease-stopping — medications, before ALS becomes debilitating.”

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