Using NfL biomarker could improve ALS diagnosis, prognosis: Study
Better accuracy found with nerve damage biomarker than other blood markers
Measuring blood levels of neurofilament light chain, or NfL, a biomarker of nerve damage, may help in diagnosing amyotrophic lateral sclerosis (ALS), and in predicting the risk of death among people with the neurodegenerative condition, a new study shows.
This biomarker showed substantially better accuracy for both ALS diagnosis and prognosis than other blood markers, the researchers noted. Further, the use of the NfL biomarker for testing is “suitable for individual assessment, unlike” other measures, the team wrote.
According to Sylvain Lehmann, MD, PhD, a coauthor of the study from the Inserm Hospital and University of Montpellier in France, “having an effective biomarker can be highly valuable” when testing individuals suspected of having ALS.
“In addition to helping in making the diagnosis, [having such a biomarker] can help in predicting prognosis, evaluating what stage of the disease people are in, and tracking their progress or their response to treatments,” Lehmann said in a press release from the American Academy of Neurology (AAN).
The study, “Comparative Performances of 4 Serum NfL Assays, pTau181, and GFAP in Patients With Amyotrophic Lateral Sclerosis,” was published in the journal Neurology, which is a publication of the AAN.
Researchers tested the biomarker NfL against 2 other proteins
Diagnosing ALS is a complex process that involves examining patients for disease-typical symptoms as well as running tests to rule out other conditions that can have similar signs and signals. When people are diagnosed with ALS, it’s also hard to predict how quickly the disease will progress.
To address these limitations, scientists have been looking for markers — particularly blood biomarkers — that can help guide ALS diagnosis and predict prognosis. To that end, “selecting the most appropriate blood tests is crucial for the management of patients with” ALS, the team wrote.
NfL is a protein that helps provide structure to nerve cells. When nerves become damaged or die, as happens in ALS, NfL protein is released into the blood and other bodily fluids. Several studies have identified NfL as a promising biomarker for ALS.
Other proteins have been proposed as potential biomarkers for ALS, such as GFAP, short for glial fibrillary acidic protein, and pTau181, or phosphorylated tau 181. GFAP is a protein that’s released when nerve-supporting cells called astrocytes become activated. The protein pTau181, meanwhile, is associated with abnormal protein clumps that occur in Alzheimer’s disease.
In this study, the researchers compared the potential utility of NfL, GFAP, and pTau181 in ALS. The team also tested four different methods to measure NfL levels, two of which are certified and routinely used in clinical settings, and two that have been widely used in research studies. The results showed that all of them performed similarly.
“We have observed that the [four] NfL assays have similar precision … and correlate exceptionally well with one another,” the researchers wrote.
Team notes need for caution in translating results to clinical practice
The study included blood samples from 139 people with ALS, as well as 70 people with neurological diseases similar to ALS.
The findings showed that NfL performed better than the other two biomarkers for diagnosing ALS. Statistical analyses indicated that NfL levels could accurately identify about 80% of ALS patients and more than 80% of people with other diseases. GFAP and pTau181, on the other hand, could only accurately identify about half of the ALS patients tested.
“NfL is proving increasingly useful in a number of clinical practice settings,” the researchers wrote in discussing the study’s findings. They added that “the data presented lay the foundation for the routine use of [NfL] tests in [clinical] practice.”
However, the team stressed that “the translation of our results into ordinary clinical practice must be approached cautiously because NfL is also indicative of many other diseases besides ALS.”
While more research needs to be done to confirm these findings, having better information about prognosis is valuable for people with ALS and their families as well as the doctors who treat them.
As part of the study, the ALS patients were followed for 3.5 years on average, while those without ALS were followed for nearly nine years. Over the course of follow-up, 85.5% of the ALS patients died, compared with 7.7% of those without the disease.
Further analyses showed that ALS patients with NfL values above a certain threshold — which was more than twice as high as the cutoff used for diagnosis — had an increased risk of mortality, according to the researchers.
Specifically, after one year of follow-up, more than 40% of ALS patients with NfL levels below that threshold were still alive, whereas all of the patients with NfL levels above the cut-off value had died. GFAP and pTau181 showed poor accuracy in predicting prognoses, the team noted.
According to Lehmann, “while more research needs to be done to confirm these findings, having better information about prognosis is valuable for people with ALS and their families as well as the doctors who treat them.”
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