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Snapshot: What is Neurofilament light protein (NfL)?

Nerve cells (aka neurons) are unique cells in that they have long, and thin extensions called axons which form connections with and talk to other neurons. This particular shape of neurons determines how quickly they can get their messages to other cells. You can think of the axons in the brain like the wires connecting all the components of a dense electrical network.

NfL stands for Neurofilament light protein (Not to be confused with the national football league!). Neurofilaments are proteins found in our neurons. They are important for helping these cells hold their structure and size. We know this is important for their ability to send messages to other neurons. NfL is the smallest unit of three types of neurofilaments (light, medium and heavy). There is a lot of NfL found in the axons of neurons.


A cortical neuron stained green with antibody to NfL. Image courtesy of GerryShaw on Wikimedia.

How do you measure NfL levels?

Like other proteins, NfL levels can be measured in fluids using tools known as immunoassays. These tools make use of antibodies generated by the immune systems to capture and count the protein of interest. It has been possible to measure NfL in cerebrospinal fluid (CSF) – the clear fluid that surrounds the brain and has lots of brain proteins – since 2005. In recent years, immunoassay technology has improved significantly, permitting the quantification of proteins previously too low in concentration to detect. One of these technologies is Single Molecule Array (Simoa) and has made it possible to measure NfL reliably in blood.

Why is NfL used as a biomarker?

Biomarkers are biological characteristics that can be measured and that tell us about a particular biological or disease process or response to a therapy. They can be used to make drug development more efficient. NfL is released into CSF after brain injury and also in many neurodegenerative diseases. This makes it a biomarker of neuronal injury. The problem with CSF is that it requires a safe but relatively invasive medical procedure called a lumbar puncture or spinal tap to collect. It would be a lot easier for both patients and doctors if we could get the same information from a blood test. Being able to quantify NfL – a brain protein – in blood, and more importantly, that it reflected what was happening in the brain was very exciting for many diseases.

In neurodegenerative diseases with effective disease modifying therapies (such as Multiple Sclerosis and Spinal Muscular Atrophy), a lowering of NfL reflects the clinical benefit in response to these therapies. In another genetic neurodegenerative disease caused by a CAG expansion, Huntington’s disease, NfL increase has been shown to be the earliest detectable change in asymptomatic gene carriers who are very far from their predicted age of disease onset. Many results like these suggest that NfL could help monitor disease even before symptoms appear, decide when to start therapies, and tell us if a drug is improving the health of neurons.

What NfL research is being done in ataxia research?

So what about ataxias? You will be pleased to know that Ataxia researchers have also jumped on the NfL band wagon. We previously wrote an article on two independently published studies in SCA3 which showed in many patients that NfL levels increased as Ataxia severity got worse, they were correlated with a measure of clinical severity (SARA) and increased with the level of brain loss (atrophy). One of the studies showed NfL levels increased with a higher number of CAG repeats in someone’s SCA3 mutation. There is also work using mouse models of SCA3 to understand this biomarker further. Two studies have now shown that NfL is also increased in Friedreich’s ataxia. With more research, NfL could potentially be used to design better clinical trials for ataxias and to monitor disease.

If you would like to learn more about NfL, take a look at this article by NeurologyLive.

Snapshot written by Dr. Lauren Byrne and edited by Dr. Gülin Öz.

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