Neurofilaments, the biomarker that could determine the progression of multiple sclerosis and other neurological diseases

In recent years, neurology has experienced significant advances in both the diagnosis and treatment of numerous diseases that until recently had virtually no treatment available, such as multiple sclerosis . One of the new tools that is helping to improve the approach to these diseases are the new biomarkers that help not only diagnose but also measure the course of the disease.

In recent years, serum neurofilament light chain (sNfL) levels have been gaining increasing relevance. As was highlighted at NeuroSummit 2025, attended by 168 specialists from all over Spain, they are becoming a very useful tool for measuring the course of multiple sclerosis (MS) and neuromyelitis optica (NMO) , and it is believed that they could be applied in many other diseases in which neuronal damage occurs, as Dr. Luisa María Villar Guimerans , head of the Immunology Service at the Ramón y Cajal University Hospital in Madrid.

What are neurofilaments and what are they used to measure?

When there is neuronal damage , as in diseases like multiple sclerosis or neuromyelitis optica, parts of the neurons pass into the cerebrospinal fluid and, to a lesser extent, into the blood, as Dr. Villar explains very graphically, "inside the neurons, there are dendrites and axons. The dendrites are the body of the neurons and the axons are a 'long tube' that connects one neuron to the next. For the axons to maintain their shape and allow neurotransmitters to pass through them, a kind of framework is needed, the cytoskeleton . When an axon breaks, that cytoskeleton destructures, among other things, into neurofilaments, which are part of that structure."

For about 10 or 15 years, several people, including Luisa María Villar Guimerans, began working on this and saw that when neurofilaments increased in the cerebrospinal fluid, which is the fluid that bathes the central nervous system, there was damage to the axons . And later, when highly sensitive methods became available, they were able to detect neurofilaments in the blood to a lesser extent, but in the same proportion. They also realized that they could detect this damage even before the patient had more symptoms. "The increase in these molecules in the blood predicts that there is damage, that inflammation, as in the case of multiple sclerosis, is causing damage to the axons. When a treatment is started and it works, it normalizes, and we no longer have damage caused by inflammation," she explains.

The increase in these neurofilaments in the blood predicts that inflammation, as in the case of multiple sclerosis, is causing damage to the axons.

To date, the use of this marker has proven useful, especially for monitoring treatments, that is, knowing whether they are working or not even before the patient has a flare-up and develops a disability that, in the case of multiple sclerosis, is irreversible. It is also a virtually non-invasive method, as it is a simple blood test , not a lumbar puncture. "The puncture to measure neurofilaments is done at the beginning, to diagnose and to see the level of damage, to know if the patient is losing axons quickly or slowly, but it is not useful for monitoring treatments because you cannot be doing lumbar punctures on patients every so often, and the MRI is done once a year," he explains.

With a blood test, on the other hand, the treatment can be monitored whenever the specialist requires it , and if it is observed that it is causing neuronal damage due to inflammation, the treatment can be changed. "Measuring this helps to choose one treatment or another depending on whether the patient is suffering from high axonal damage . And once the treatment has been chosen, it is to monitor the patient and see how it is working. If it works, you stop it, but if it is observed that there is high neuronal damage, you can change to another, even before the patient notices it physically or has an outbreak, you get ahead of the clinical situation, you detect it before the patient gets worse. You can anticipate the patient becoming disabled , because before we could only know that the treatment was not working when the patient had symptoms, had outbreaks, had a disability...," he assures, "and this is something very novel and very important."

In the case of neurodegenerative diseases , such as MS or NMO, this is very important, as treatments are available and they occur in flares that cause accumulating disability. Avoiding a flare means, in the long term, avoiding or delaying much of the disability. "This biomarker allows us to detect the damage associated with acute inflammation, because when there is acute damage, neurofilaments increase," he explains.

It can detect if there is elevated neuronal damage even before the patient notices it or has an outbreak, before it worsens

Just the tip of the iceberg

Neurofilament measurement is increasingly being used in the treatment of multiple sclerosis, but the goal of researchers like Dr. Luisa María Villar Guimerans is for it to become more widespread. "At the moment, it's not done everywhere, but its use is becoming more widespread due to how useful it is. You need the equipment to do it, but our intention is for it to be increasingly implemented in clinical practice," she explains.

In the future, he doesn't rule out the possibility of it even being used to diagnose some cases, but further studies are needed. "We have other tests for diagnosis, but I do know that it could be used in the future in some cases. For example, in health centers, when a patient is seen with a suspicion, performing this test could bring those suspicions closer together and refer the patient to a specialist more quickly, but this is being studied; it hasn't been included in the latest diagnostic criteria because we don't have enough evidence yet," he acknowledges.

There are still many studies missing, but if there is one thing that Dr. Luisa María Villar is quite certain of, it is that this biomarker is going to give a lot to talk about in the coming years, and not only in these two diseases, "neurofilaments speak of axonal damage, and there is not only axonal damage in multiple sclerosis and neuromyelitis optica. The clearest data we have in these diseases, but now work is being done in other pathologies such as ALS , Parkinson's , Alzheimer's ... where we hope that, together with other proteins that are being studied, both in the cerebrospinal fluid and in the serum, they will help us evaluate the follow-up and see how the patients evolve . We are sure that what happened in multiple sclerosis is just the tip of the iceberg and that soon this will be used in other neurological pathologies", she assures optimistically.

This tip of the iceberg could even go beyond neurological diseases , also to diseases that cause damage at the level of the central nervous system , at the brain level, at the bone marrow level... and they are already, in fact, testing it in patients with Alzheimer's, "this is of great interest, because until now we had nothing that told us that there was damage to the central nervous system in blood , with a blood test, which is something easy to do, which is why the history of neurofilaments is only just beginning, which will have many applications. We are already seeing something in the treatments of some cancers, and we are sure that this is only the beginning. In Spain we have been lucky to play a pioneering role in these studies and we are very happy with the work we are doing, because we believe that it will help a lot to avoid disability . At the moment, in patients with multiple sclerosis, and a very broad field of research opens up in other pathologies."