NfL as a biomarker for neurodegeneration and survival in Parkinson disease

Neurology. 2020 Aug 18;95(7):e827-e838. doi: 10.1212/WNL.0000000000010084. Epub 2020 Jul 17.

Abstract

Objective: To determine whether neurofilament light chain protein in CSF (cNfL), a sensitive biomarker of neuroaxonal damage, reflects disease severity or can predict survival in Parkinson disease (PD).

Methods: We investigated whether disease severity, phenotype, or survival in patients with new-onset PD correlates with cNfL concentrations around the time of diagnosis in the population-based New Parkinsonism in Umeå (NYPUM) study cohort (n = 99). A second, larger new-onset PD cohort (n = 194) was used for independent validation. Association of brain pathology with the cNfL concentration was examined with striatal dopamine transporter imaging and repeated diffusion tensor imaging at baseline and 1 and 3 years.

Results: Higher cNfL in the early phase of PD was associated with greater severity of all cardinal motor symptoms except tremor in both cohorts and with shorter survival and impaired olfaction. cNfL concentrations above the median of 903 ng/L conferred an overall 5.8 times increased hazard of death during follow-up. After adjustment for age and sex, higher cNfL correlated with striatal dopamine transporter uptake deficits and lower fractional anisotropy in diffusion tensor imaging of several axonal tracts.

Conclusions: cNfL shows usefulness as a biomarker of disease severity and to predict survival in PD. The present results indicate that the cNfL concentration reflects the intensity of the neurodegenerative process, which could be important in future clinical trials.

Classification of evidence: This study provides Class II evidence that in patients with PD, cNfL concentrations are associated with more severe disease and shorter survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Diffusion Tensor Imaging / methods
  • Disease Progression
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurofilament Proteins / metabolism*
  • Parkinson Disease / diagnosis*
  • Parkinson Disease / metabolism
  • Parkinsonian Disorders / diagnosis*

Substances

  • Biomarkers
  • Dopamine Plasma Membrane Transport Proteins
  • Neurofilament Proteins