Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting nerve cells in the brain and spinal cord, leading to loss of muscle control. Currently, there is no single, definitive blood test used in standard clinical practice to diagnose ALS. Diagnosis remains a process of clinical observation and exclusion. However, the search for a blood test is an active area of research, and recent scientific discoveries suggest a definitive test may be available soon.
Current Methods for Diagnosing ALS
Confirming an ALS diagnosis is lengthy and relies heavily on a neurologist’s clinical judgment. Diagnosis requires observing progressively worsening signs of both upper motor neuron involvement (in the brain) and lower motor neuron involvement (in the spinal cord and brainstem). Since symptoms like muscle weakness can mimic several other conditions, the diagnostic process involves systematically ruling out diseases such as multiple sclerosis or spinal cord compression.
This process of elimination often utilizes specialized electrodiagnostic tests, primarily the nerve conduction study (NCS) and electromyography (EMG). The NCS measures the speed and strength of electrical signals through the motor and sensory nerves. In ALS, the sensory nerve response is typically normal, which helps distinguish it from other neuropathies.
The EMG directly assesses the health of lower motor neurons and the muscles they control. A small needle electrode inserted into muscles detects abnormal electrical activity, such as fibrillation potentials and fasciculation potentials, which signify active motor neuron degeneration. Neurologists use these electrodiagnostic results, combined with a comprehensive physical and neurological exam, to meet established diagnostic criteria, a process that often takes many months. Imaging studies, like magnetic resonance imaging (MRI), are performed not to confirm ALS, but to ensure symptoms are not caused by a structural lesion or another neurological disorder.
The Ongoing Search for Blood Biomarkers
The search for a reliable blood test focuses on identifying a biomarker, a measurable biological indicator of a disease state. The most promising candidates are neurofilaments, structural proteins found inside nerve cells. When motor neurons are damaged in ALS, these neurofilaments are shed, and their fragments leak into the cerebrospinal fluid and eventually into the bloodstream.
Researchers primarily measure two types: neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH). Elevated levels of NfL and pNfH in blood correlate with the extent of active neuronal damage and can help distinguish ALS from healthy controls or other neurological conditions. Although not a standalone diagnostic test, neurofilament measurement is increasingly used in research to track disease progression and monitor treatment efficacy.
Beyond neurofilaments, scientists are investigating complex protein signatures and genetic indicators in the blood. Recent studies have utilized advanced proteomic techniques, analyzing thousands of proteins in a single blood sample, to identify distinct protein patterns specific to ALS. One study identified a signature of 33 proteins that could differentiate ALS patients with high accuracy. Other research focuses on microRNA sequences, small molecules that regulate gene expression, found in tiny vesicles released by nervous system cells. These novel approaches have demonstrated over 97% accuracy in research settings, and some protein changes have been detected in blood samples collected up to a decade before the onset of clinical symptoms, suggesting potential for pre-symptomatic detection.
Why a Definitive Blood Test Is Critical
Developing a simple, definitive blood test for ALS is a high priority for clinical care and research. Patients currently experience a significant diagnostic delay, typically 10 to 12 months from symptom onset to confirmed diagnosis. This extended period is lost time for intervention, as the progressive nature of ALS means motor neurons are continuously being lost.
An accurate blood test would immediately reduce this diagnostic delay, allowing patients to start disease-modifying therapies sooner. Treatments like riluzole and edaravone, which slow disease progression, are most effective when administered early. A reliable, objective blood test is crucial for advancing clinical trials.
A blood biomarker could serve as a surrogate endpoint, offering a faster, measurable way to determine if a new drug is working by showing a reduction in the biomarker level, such as NfL. This capability would streamline drug development, accelerating the search for more effective therapeutic options. Identifying patients in the earliest or pre-symptomatic stages of ALS would revolutionize treatment and research opportunities.