Higher Levels of Neurofilament Light Protein Tied to Cognitive Impairment, Neurodegeneration

December 5, 2018

By Will Boggs MD 

NEW YORK—Higher levels of neurofilament light (NFL) protein in the cerebrospinal fluid (CSF) are associated with cognitive impairments in patients with dementia and neurodegeneration intensity in patients with other neurodegenerative disorders, researchers report.

"NFL may help to separate different forms of neurodegenerative diseases from each other and cognitive decline from other causes than neurodegeneration, e.g., depression or drug-related side effects," said Dr. Bob Olsson of the University of Gothenburg, Sahlgrenska University Hospital Molndal, in Molndal, Sweden.

"NFL may also be used as a marker of disease severity," he told Reuters Health by email.

NFL protein is released into the CSF during axonal damage and has been shown to be elevated in dementia and amyotrophic lateral sclerosis (ALS). Its usefulness in understanding neurodegenerative disease is not yet clear.

Dr. Olsson and colleagues analyzed NFL levels in CSF from 75 healthy controls and 845 patients with clinical diagnoses of neurodegenerative disorders, including mild cognitive impairment (MCI), Alzheimer disease, frontotemporal dementia (FTD), ALS, Parkinson's disease with normal cognition or MCI or dementia, dementia with Lewy bodies (DLB), corticobasal syndrome (CBS), or progressive supranuclear palsy (PSP).

CSF levels of NFL were significantly increased, compared with controls, in participants with MCI, Alzheimer disease and other forms of dementia, and the highest levels of NFL were observed in patients with ALS, followed by participants with Alzheimer disease, FTD, DLB, and Parkinson disease with dementia.

NFL levels were elevated in most patients with neurodegenerative diseases, the researchers note.

NFL levels significantly improved the ability of a three-biomarker panel to discriminate between various disorders. For example, it boosted the accuracy of discrimination between ALS and most other forms of neurodegenerative disorders.

CSF levels of NFL correlated significantly with annual worsening in cognitive performance in patients with Alzheimer disease or FTD, but not in patients with MCI, the researchers report in JAMA Neurology, online December 3.

NFL levels correlated with the severity of transactive response DNA-binding protein (TDP)-43 in 13 of 17 brain regions, further supporting the usefulness of NFL measurement in correctly diagnosing ALS and FTD, both of which are linked to TDP-43 inclusions.

"It is important to analyze biomarkers in the cerebrospinal fluid and not only rely upon psychological testing," Dr. Olsson said. "Anyone can have a bad day when it comes to psychological testing, but you do not have a bad day when it comes to biomarkers. Furthermore, repeated sampling over time allows you to more objectively follow potential progression than interview-based tests alone."

He added, "Once treatments for these diseases are available, NFL will be a key marker to follow treatment response."

Dr. Mathias Jucker of the University of Tuebingen, in Germany, who earlier reported on blood and CSF levels of NFL as markers of disease progression in mouse models and in neurodegenerative diseases, told Reuters Health by email, "The study is nicely done but mostly repetitive of many previous publications. The next step is to do it longitudinally and in blood, but this has not been done here."

"We and others have such results in press," he said, adding that he expects his paper to appear in Nature Medicine within the next several weeks.

SOURCE: https://bit.ly/2QDAfrA

JAMA Neurol 2018.

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