Neurofilament: The traitorous component of nerve cells

Neurofilaments are among the building materials that make up the so-called cytoskeleton—essentially the shell that gives nerve cells their shape and stability. These string-like proteins are released when nerve cells are remodeled or damaged, which is always the case in neurodegenerative diseases. They then enter the blood and cerebrospinal fluid, where their concentration provides information about how the disease is progressing and whether a chosen treatment is working.

Neurofilament has little to do with the disease itself. It merely serves as a biomarker – i. e., a measurable indicator – for the disease processes taking place in the brain. It is ideally suited for this purpose because it can be detected in a simple blood sample with minimal technical effort. Neurofilament levels are already routinely measured in patients with Alzheimer's disease at memory clinics; this biomarker is also used in other diseases such as Parkinson's or ALS.

The dynamics of the biomarker level are what matters

It's been known for a while that high levels of neurofilament can be measured in the blood of people with neurodegenerative diseases. In 2019, researchers at the DZNE managed to measure the correlation with disease progression. To do this, they used biological samples from volunteers that had been collected over decades. These samples showed how neurofilament levels rose steadily many years before the onset of Alzheimer's disease. The development of neurofilament concentration therefore allows conclusions to be drawn about the stage of the disease, even if it is still asymptomatic.

The absolute amount of neurofilament in the blood is not decisive, as a certain amount of it is also found in healthy young people; instead, the researchers pay attention to changes in the level. The rate of increase allows important conclusions to be drawn about the stage of the disease, as this increase follows a characteristic pattern in ALS, Alzheimer's, and Parkinson's.

The construction plan of the cytoskeleton

There are three types of neurofilaments in nerve cells, which are classified as light, medium, and heavy according to their molecular weight. The light neurofilament, also abbreviated as NfL (neurofilament light), serves as a biomarker. The cytoskeleton also includes actin filaments and microtubules, two other structural components. These are also released when nerve cells die; however, NfL is particularly easy to detect in the blood and is broken down slowly, making it easy to measure.

Drug development is an important field in which scientists are working with neurofilaments. When a drug for a neurodegenerative disease is tested on patients, regular monitoring of neurofilament levels reveals whether the treatment is working or not. If successful, the neurofilament concentration decreases or at least does not rise any further.