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Testing a blood biomarker for neurodegeneration

From NIH Research Matters

Neurodegenerative diseases cause progressive damage and death to nerve cells. This leads to problems in thought, attention, and memory. Reliable and accessible biomarkers would enable the early diagnosis and treatment of such diseases.

Scientist’s hands, wearing purple gloves, looking at many different laboratory blood collection tubes.
A blood test for neurodegeneration would allow doctors to begin treatments early, when they’re likely to be more effective.

One potential biomarker is a protein called neurofilament light chain (NfL). NfL is released when nerve cells are damaged. Elevated NfL concentrations are found in cerebrospinal fluid (CSF) in most neurodegenerative disorders. But CSF collection is an invasive procedure. This limits the use of CSF NfL for routine diagnosis.

NfL concentrations in blood correlate strongly with those in CSF. This suggests that blood NfL could be a less invasive biomarker. Toward this end, a research team led by Drs. Nicholas Ashton, Abdul Hye, and Oskar Hansson—based at the University of Gothenburg, King’s College London, and Lund University in Sweden—measured blood NfL concentrations in more than 2,200 people. The team also included scientists from NIH’s National Institute on Aging (NIA).

The study participants came from Europe, Canada, and the U.S. They included people with 13 neurodegenerative disorders, Down syndrome, and depression. Unimpaired controls were also included. Results appeared in Nature Communications on June 7, 2021.

The researchers found elevated NfL concentrations in people with various forms of dementia. They also found elevated NfL concentrations in those with amyotrophic lateral sclerosis (Lou Gehrig’s disease) and atypical parkinsonian disorders.

NfL concentrations were not disease-specific. Thus, NfL alone could not distinguish between different types of cognitive disorders. But it could aid in diagnosing patients. For example, NfL concentrations could distinguish Parkinson’s disease from atypical parkinsonian disorders such as multiple system atrophy, corticobasal syndrome, and progressive supranuclear palsy. Among people with Down Syndrome, NfL could distinguish those with and without dementia.

NfL could also distinguish moderate and severe depression from neurodegenerative disorders with 90% accuracy or greater. This is important because certain neurodegenerative diseases, such as frontotemporal dementia, cause psychiatric symptoms like depression and anxiety. NfL could help determine whether a patient with depression has such a disease.

The researchers determined threshold NfL levels for determining whether a patient had neurodegeneration. Using separate thresholds for people older and younger than 65 years of age improved the diagnostic accuracy. In all age groups, the researchers found accurate thresholds for diagnosing neurodegeneration. Diagnosis based on these thresholds yielded very few false positives.

The results suggest that blood tests for NfL could be used to detect neurodegenerative diseases in the clinic. “For the first time we have shown across a number of disorders that a single biomarker can indicate the presence of underlying neurodegeneration with excellent accuracy,” Hye says. “Though it is not specific for any one disorder, it could help in services such as memory clinics as a rapid screening tool to identify whether memory, thinking, or psychiatric problems are a result of neurodegeneration.”

by Brian Doctrow, Ph.D.

This study was supported in part by the Intramural Research Program at the National Institute on Aging.

Reference: A multicentre validation study of the diagnostic value of plasma neurofilament light. Ashton, N.J., Janelidze, S., Al Khleifat, A. et al. Nat Commun.2021 Jun 7;12(1):3400. doi: 10.1038/s41467-021-23620-z. PMID:34099648.