NFL levels also boosted ability to discern between certain disorders
Neurofilament light protein levels in cerebrospinal fluid (CSF) were tied to cognitive impairment in dementia patients and neurodegeneration intensity in other disorders, researchers reported.
And adding it to a three-biomarker panel -- consisting of 42-residue amyloid beta protein (AB-42), total tau, and phosphorylated tau -- improved its ability to discriminate among certain neurodegenerative disorders for which the differential diagnosis is often difficult, according to Bob Olsson, MD, PhD, of the University of Gothenburg in Sweden, and co-authors, in JAMA Neurology.
"Neurofilament light levels reflect cognitive dysfunction in patients with Alzheimer's disease and frontotemporal dementia (FTD)," Olsson told MedPage Today. "It may help to separate different forms of neurodegenerative diseases from each other and cognitive decline from other causes than neurodegeneration, such as depression or drug-related side effects."
Neurofilament light protein previously has been shown to be elevated in different forms of dementia and amyotrophic lateral sclerosis (ALS). Although other studies have shown similar findings, "this study is the most exhaustive to date and includes a much larger sample size and a wider range of neurodegenerative diseases to compare CSF neurofilament light levels," noted Michelle Mielke, PhD, of the Mayo Clinic in Rochester, Minnesota, who was not involved with the study.
"It is notable that the addition of CSF neurofilament light to CSF amyloid-beta, total tau, and phosphorylated tau greatly increased the accuracy of distinguishing ALS or FTD patients compared to controls," Mielke told MedPage Today. "However, it is not yet clear how much the addition of CSF neurofilament light to the other CSF biomarkers will help with differentially diagnosing the specific type of neurodegenerative disease."
In this study, Olsson and co-authors analyzed neurofilament light levels in CSF samples from 913 people with an average age of about 69. The group included 75 healthy controls and 845 patients with clinical diagnoses of neurodegenerative disorders including mild cognitive impairment (n=114), Alzheimer's disease (n=397), FTD (n=96), ALS (n=68), Parkinson's disease (n=41), Parkinson's disease with mild cognitive impairment (n=19), Parkinson's disease with dementia (n=29), dementia with Lewy bodies (n=33), corticobasal syndrome (n=21), and progressive supranuclear palsy (n=20).
Mini-Mental State Examination (MMSE) scores were analyzed every 6 months for most patients, and autopsy-verified diagnoses were available for 120 of the 845 patients with diseases.
Neurofilament light levels were elevated in a stepwise manner, with the lowest levels in control participants, significantly higher levels in patients with mild cognitive impairment, and even higher levels in Alzheimer's disease. Although the highest levels were observed in patients with ALS and the second-highest levels in those with FTD, neurofilament light concentrations were elevated in Parkinson's disease with dementia, dementia with Lewy bodies, corticobasal syndrome, and progressive supranuclear palsy patients, compared with controls.
Neurofilament light levels rose with increasing cognitive impairment, with higher levels in Alzheimer's patients, intermediary levels in patients with mild cognitive impairment, and lowest levels in controls. They correlated significantly with annual worsening in cognitive performance on MMSE in patients with Alzheimer's or FTD, but not in patients with mild cognitive impairment. They also were tied to the severity of transactive response DNA-binding protein-43 in 13 of 17 brain regions.
Adding neurofilament light to the three-biomarker panel of AB-42, total tau, and phosphorylated tau led to:
- 29% (95% CI 25.0%-33.3%) increase in accuracy in distinguishing between controls and ALS, from 62% to 91%
- 17% (95% CI 14.9%-19.5%) increase between controls and the behavioral variant of FTD, from 63% to 81%
- 14% (95% CI 8.7%-19.1%) increase between Parkinson's disease and progressive supranuclear palsy, from 62% to 76%
"Future studies with serially-collected samples across the neurodegenerative diseases will be useful for understanding how CSF neurofilament light tracks with the progression of each disease," noted Mielke.
The study has a number of limitations: some subgroups have small sample sizes, and the risk of false-positive statistical test results warrants replication of the findings, the authors noted. While the MMSE is not a strong indicator of disease severity for FTD, it was the only measure of cognition available for all FTD patients.
The study was supported by grants from the Swedish and European Research Councils, the Torsten Söderberg Foundation, the Swedish Brain Foundation, the Knut and Alice Wallenberg Foundation, Frimurarestiftelsen, Stiftelsen för Gamla Tjänarinnor, Foundation for Research on Alzheimer, the Swedish Alzheimer Foundation, and Swedish State Support for Clinical Research in addition to the National Institutes of Health.
Researchers reported relationships with Merck, Biogen, Avid Radiopharmaceuticals, Eli Lilly, GE Healthcare, Janssen, Brain Biomarker Solutions, Roche Diagnostics, Teva, Alzheon, BioArctic, Fujirebio Europe, IBL International, and Pfizer.
https://www.medpagetoday.com/neurology/generalneurology/76807
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