Neurofilaments are proteins inside nerve cells (neurons) that help give structural strength to the cell, particularly in the long extensions called axons that carry nerve signals.
When nerve cells are damaged, neurofilament proteins leak out and enter the cerebrospinal fluid (CSF) – the clear fluid around the brain and spine - and from there go into the bloodstream. Neurofilament Light Chains (NfLs) are one of these proteins.
Measuring NfL levels in the blood or CSF can show whether nerve cell damage is occurring. Higher NfL levels suggest damage or degeneration somewhere in the nervous system, but the test cannot show where the damage is occurring or what is causing it.
NfL testing is relatively new. In the past, measuring NfLs in the blood has been difficult mainly because only very small amounts reach the bloodstream. Doctors relied on brain imaging and CSF analysis, which requires an invasive procedure called a lumbar puncture (spinal tap).
Older laboratory methods were not sensitive enough to reliably detect NfLs but now we have newer highly sensitive laboratory assays.
Blood testing for NfL has only become possible recently with the development of highly sensitive laboratory techniques that can detect the tiny amounts of NfL present in the bloodstream. NfL blood tests require a routine blood sample, making testing simpler and less invasive than a CSF collection.
NfL testing is mostly used to investigate and monitor Multiple Sclerosis (MS) or to assess someone with memory problems, cognitive decline or suspected dementia.
NfL levels often rise before symptoms appear or worsen, making the test useful for detecting nerve cell damage at an early stage. This can help identify disease activity sooner and monitor how a condition is changing over time. In some disorders, an increase in NfL may provide an early warning of a relapse or new nerve damage before symptoms become noticeable. Repeat testing can show whether nerve damage is worsening, remaining stable, or improving.
Multiple Sclerosis (MS)
Measuring NfL levels can help show whether MS activity is being controlled, whether treatment is working, or whether a change in treatment may be needed. It can also provide information about the likely risk of future disease activity. Persistently raised NfL levels may indicate a greater risk of future relapses. NfL testing can also provide additional information when MRI results are unclear or do not match a person’s symptoms.
International guidelines recommend measuring blood NfL at diagnosis to establish a baseline, then repeating the test every 6–12 months, or after a relapse or change in treatment.
NfL results are interpreted alongside symptoms, clinical assessment, imaging and other investigations. They are not used alone to make treatment decisions.
Cognitive impairment/ suspected dementia
NfL testing may be used when someone has symptoms such as memory loss, confusion, difficulty thinking, changes in behaviour or trouble managing everyday activities. The test can help show whether these symptoms are linked to nerve cell damage in the brain.
NfL levels are usually interpreted alongside the results of other blood tests, particularly p-tau181 or p-tau217. NfL is a general marker of nerve cell damage, while p-tau and amyloid biomarkers provide more specific evidence of the brain changes associated with Alzheimer’s disease. A normal NfL result makes active neurodegeneration less likely but does not completely exclude Alzheimer's disease or other neurological conditions.
Amyotrophic lateral sclerosis (ALS)
High NfL levels are often found in people with amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease (MND). Where ALS is suspected, NfL testing may help distinguish ALS from conditions with similar symptoms and may provide information about how quickly the disease is progressing.
Parkinson’s disease
NfL testing may help distinguish Parkinson’s disease from other conditions that cause similar Parkinson-like symptoms. It may also provide useful information when assessing other brain disorders, including frontotemporal dementia.
Other neurological conditions
NfL levels can be raised in many different conditions that cause damage to nerve and brain cells including:
Although NfL is increased in many neurological disorders, it cannot diagnose a specific condition on its own and must always be interpreted together with symptoms, examination findings and other investigations.
Sample:
Blood.
Some laboratories can also measure NfL in cerebrospinal fluid (CSF), although blood testing is now used much more commonly.
Any preparation?
None.
While NfL is not diagnostic of any single condition, measuring can provide useful information regarding disease activity, progression, and treatment response.
NfL is a general marker of nerve cell injury. The higher the level, the more nerve damage is occurring, but the result must always be interpreted in the context of other information such as:
Reference intervals
Many blood tests results are compared to reference intervals (sometimes called a normal range). Reference intervals are the range of results expected in healthy people. When compared against them your results may be flagged as being high or low if they sit outside this range.
Reference intervals for NfL tests are complicated. With NfL tests, laboratories generally use age-adjusted clinical decision limits or age-specific reference percentiles rather than a single reference interval. These cut-offs are age adjusted because NfL levels rise with age. For example, a level that is normal for an 80-year-old might be considered high in a 30-year-old.
| Result | Possible Meaning |
| Below age specific cut-off | No evidence of significant active nerve cell injury. |
| Above age specific cut-off | Suggests active nerve cell injury. Further assessment is needed to determine the cause. |
NfL reference ranges can vary between laboratories because different testing methods are used. This means that the numbers on a test report may differ from one laboratory to another, and results cannot be compared directly.
Terms you might come across
You might see terms on your report such as:
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