Amyotrophic Lateral Sclerosis (ALS) is a serious disease that affects the neurons responsible for body movement, leading to progressive loss of muscle strength. Diagnosis can be difficult, but researchers have discovered that the protein NfL, found in the blood, can help identify the disease more accurately and predict its progression.
Amyotrophic Lateral Sclerosis (ALS) is a serious neurodegenerative disease that affects the motor neurons responsible for controlling body movement.
As the disease progresses, patients gradually lose the ability to move their muscles, leading to weakness, difficulty speaking, swallowing and, eventually, breathing. Unfortunately, ALS progresses rapidly and significantly impacts life expectancy.
Diagnosing Amyotrophic Lateral Sclerosis can be quite difficult, as its initial symptoms can resemble those of other neuromuscular diseases. In some cases, patients are misdiagnosed with Amyotrophic Lateral Sclerosis and later discover that they have a slower-progressing condition.
Therefore, it is essential that the diagnosis is as accurate as possible to avoid mistakes and ensure the best treatment from the beginning.
Neurological biomarkers are substances in the body that help doctors diagnose diseases, predict their progression, and monitor the effects of treatments. In recent years, major scientific advances have allowed these biomarkers to be detected directly in the blood, without the need for more invasive tests such as a spinal tap.
This advance is especially useful for neurodegenerative diseases such as Amyotrophic Lateral Sclerosis, where finding less aggressive diagnostic methods is essential.
One promising biomarker for Amyotrophic Lateral Sclerosis is neurofilament light chain (NfL) protein, which is part of the structure of neurons and is released into the blood when there is damage to the nervous system.
Elevated levels of neurofilament light chain protein indicate neuronal distress, which can occur not only in Amyotrophic Lateral Sclerosis, but also in other neurological diseases such as Alzheimer's, multiple sclerosis, and traumatic brain injuries.
Studies have shown that measuring neurofilament light chain protein in the blood can help differentiate ALS from other conditions and also predict the rate of disease progression. Compared to other biomarkers used to assess neuronal degeneration, neurofilament light chain protein has been shown to perform better.
Despite its usefulness, there are still challenges to adopting neurofilament light chain protein as a standard test in the diagnosis of ALS.
Different laboratories use different methods to measure this protein, and there is still no consensus on the exact values that define whether a patient has ALS or not.
To address this issue, studies are comparing different measurement techniques to ensure that the results are reliable and can be applied in daily medical practice.
Researchers have already compared two advanced methods for measuring neurofilament light chain protein in the blood, known as Simoa and Ella, and found that both are effective in diagnosing and predicting the progression of Amyotrophic Lateral Sclerosis.
However, the Simoa method, despite being very sensitive, is not yet ready for routine use as a clinical test.
To make this analysis more accessible to doctors and patients, new studies have included two other methods: Lumipulse and Elecsys, which are technologies more compatible with use in conventional hospitals and laboratories.
Lumipulse Automated Immunoassay Analyzer
In addition to neurofilament light chain protein, the researchers tested two other biomarkers: GFAP (glial fibrillary acidic protein) and pTau181 (phosphorylated tau 181). GFAP is linked to inflammation in the brain and may be a useful marker for neurodegenerative diseases.
pTau181 is a protein associated with Alzheimer's disease, and some studies suggest that its levels may help differentiate ALS from other diseases that affect motor neurons.
To test these biomarkers, a study was conducted with 139 patients with ALS and 70 patients without the disease, aged around 66 years. The participants were followed for more than 40 months, and the researchers analyzed the relationship between the levels of these proteins and the progression of the disease.
The results showed that all methods tested to measure neurofilament light chain protein showed high accuracy in diagnosing Amyotrophic Lateral Sclerosis, while glial fibrillary acidic protein and pTau181 performed less effectively.
In addition, the researchers observed that high levels of neurofilament light chain protein were directly associated with a shorter life expectancy in patients with Amyotrophic Lateral Sclerosis.
In cases where protein levels were very high, the chances of survival after 50 weeks were practically zero. It was also identified that the age and body mass index of the patients influenced the levels of these proteins, which may be a factor to be considered when interpreting the test results.
In summary, the study demonstrated that neurofilament light chain protein in the blood can be a reliable biomarker for diagnosing and predicting the progression of Amyotrophic Lateral Sclerosis, allowing doctors to identify the disease more quickly and accurately.
This could be a major breakthrough for patients, who will have a more accurate diagnosis and will be better prepared for treatment and the challenges of the disease. The researchers suggest that the Lumipulse and Elecsys platforms could be incorporated into medical practice, making this test more accessible for clinical use.
READ MORE:
Comparative Performances of 4 Serum NfL Assays, pTau181, and GFAP in Patients With Amyotrophic Lateral Sclerosis
Etienne Mondesert, Constance Delaby, Elisa De La Cruz, Jens Kuhle, Pascal Benkert, Nicolas Pradeilles, Marie Duchiron, Mehdi Morchikh, William Camu, Jean-Paul Cristol, Christophe Hirtz, Florence Esselin and Sylvain Lehmann
Neurology. 104 (6). 26 February 2025.
DOI: 10.1212/WNL.0000000000213400
Abstract:
Selecting the most appropriate blood tests is crucial for the management of patients with amyotrophic lateral sclerosis (ALS). This study evaluates the diagnostic and prognostic performance of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau 181 (pTau181) biomarkers in ALS to establish their clinical relevance and cutoff values. In a cohort of patients from the ALS center in Montpellier, we conducted a head-to-head comparison of 4 different technologies and 3 distinct serum analytes: NfL was tested using the ultrasensitive Simoa and the microfluidic Ella platforms, along with 2 assays recently set up on clinical-grade platforms: Lumipulse and Elecsys. We also used Elecsys to assess serum GFAP and pTau181. Our cohort included 139 patients with ALS and 70 non-ALS patients, with a mean age of 66.1 ± 11.4 years and 47.4% of women. The mean follow-up was 42 ± 26.3 months for patients with ALS and 141.6 ± 106.3 months for non-ALS patients, with a mortality rate of 85.5% vs 7.7%. There was a high correlation between all methods tested for serum NfL quantification (R2 = 0.939 to 0.963). The area under the curve (AUC) for ALS diagnosis was 0.889 (0.827–0.932) for NfL Simoa, 0.906 (0.847–0.944) for Ella, 0.912 (0.853–0.948) for Lumipulse, and 0.910 (0.851–0.946) for Elecsys. Serum pTau181 and GFAP showed poor diagnostic performance with AUCs of 0.565 (0.472–0.649) and 0.546 (0.461–0.636), respectively. Kaplan-Meier survival analysis revealed significant hazard ratios (4.4–5.4) for blood NfL. Patients with ALS had a 40%–50% chance of surviving 50 weeks below the prognostic cutoff values while survival rates dropped to near zero above. NfL and GFAP levels were associated with age and body mass index, considered confounding factors. pTau181 levels varied significantly in patients with ALS depending on the site of onset. This study demonstrates the consistent performance of 4 immunoassays for serum NfL quantification in ALS. NfL showed high diagnostic and prognostic accuracy, making it suitable for individual assessment, unlike GFAP or pTau181. We propose diagnostic and prognostic cutoff values for serum NfL, providing a basis for wider implementation, especially with the clinically accredited Lumipulse and Elecsys platforms, which are becoming standard practice. This study provides Class II evidence that serum NfL levels are useful in identifying over 80% of patients with ALS and predicting survival in patients with ALS compared with pTau181 and GFAP levels.
Comments