Olsson B, et al. - Researchers investigated the utility of cerebrospinal fluid neurofilament light (CSF NFL) as a general marker of neurodegeneration. Further, they determined its association with disease progression. In this case-control study, patients with Alzheimer disease and frontotemporal dementia displayed an association between levels of CSF NFL and cognitive impairments. NFL levels seemed reflecting the intensity of the neurodegenerative processes in other neurodegenerative disorders.

Methods

• NFL levels were determined in CSF obtained from controls and patients with several neurodegenerative diseases.
• Between 1996 and 2014, samples were collected; patients were followed up longitudinally for cognitive testing, and a portion were autopsied in a single center (University of Pennsylvania).
• Data analysis was performed throughout 2016.
• Researchers assessed levels of CSF NFL and correlations with cognition scores as main outcomes and measures .

Results

• Researchers included 913 participants (mean [SD] age, 68.7 [10.0] years; 456 [49.9%] women) in this study: 75 control participants plus 114 patients with mild cognitive impairment (MCI), 397 with Alzheimer disease, 96 with frontotemporal dementia, 68 with amyotrophic lateral sclerosis, 41 with Parkinson disease (PD), 19 with PD with MCI, 29 with PD dementia, 33 with dementia with Lewy bodies, 21 with corticobasal syndrome, and 20 with progressive supranuclear palsy.
• For 1 to 18 years, they performed cognitive testing follow-up (mean [SD], 0.98 [2.25] years); for 120 of 845 participants with diseases, autopsy-verified diagnoses were available (14.2%).
• CSF NFL levels increased stepwise among control participants (median [range] score, 536 [398-777] pg/mL), participants with MCI (831 [526-1075] pg/mL), and those with Alzheimer disease (951 [758-1261] pg/mL), indicating that NFL levels increase with increasing cognitive impairment.
• They noted an inverse link of levels of NFL with baseline Mini-Mental State Examination scores (ρ, −0.19; P < .001) in the full cohort (n = 822) and annual score decline in the full cohort (ρ, 0.36, P < .001), participants with AD (ρ, 0.25; P < .001), and participants with FTD (ρ, 0.46; P=.003).
• Participants with amyotrophic lateral sclerosis (median [range], 4185 [2207-7453] pg/mL) and frontotemporal dementia (2094 [230-7744] pg/mL) displayed the highest concentrations of NFL.
• Among individuals with parkinsonian disorders, those with progressive supranuclear palsy (median [range], 1578 [1287-3104] pg/mL) and corticobasal degeneration (1281 [828-2713] pg/mL) displayed the highest NFL concentrations.
• In the full cohort, the NFL concentrations in CSF correlated with TDP-43 load in 13 of 17 brain regions.
• Accuracy of discrimination of diseases was increased with the addition of NFL to β-amyloid 42, total tau, and phosphorylated tau.