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Patients with Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases Have Increased Levels of Neurofilament Protein in CSF
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1996
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The study developed an ELISA to quantify the light subunit of neurofilament protein (NFL) in cerebrospinal fluid. The assay was validated by measuring NFL levels in CSF from healthy controls and patients with amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). CSF NFL concentrations were markedly higher in ALS and AD patients than in controls, were higher in ALS patients with upper motor neuron signs than those with only lower motor neuron signs, and were also elevated in a range of other neurodegenerative disorders, indicating that CSF NFL may serve as a general biomarker of neurodegeneration, particularly in ALS involving the pyramidal tract.
Abstract: In the present study we describe an ELISA to quantify the light subunit of the neurofilament triplet protein (NFL) in CSF. The method was validated by measuring CSF NFL concentrations in healthy individuals and in two well‐characterized groups of patients with amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). The levels were increased in ALS (1,743 ± 1,661 ng/L; mean ± SD) and AD (346 ± 176 ng/L) compared with controls (138 ± 31 ng/L; p < 0.0001 for both). Within the ALS group, patients with lower motor neuron signs only had lower NFL levels (360 ± 237 ng/L) than those with signs of upper motor neuron disease (2,435 ± 1,633 ng/L) ( p < 0.05). In a second study patients with miscellaneous neurodegenerative diseases were investigated (vascular dementia, olivopontocerebellar atrophy, normal pressure hydrocephalus, cerebral infarctions, and multiple sclerosis), and the CSF NFL level was found to be increased (665 ± 385 ng/L; p < 0.0001). NFL is a main structural protein of axons, and we suggest that CSF NFL can be used to monitor neurodegeneration in general, but particularly in ALS with involvement of the pyramidal tract.