Serum Neurofilament Light Chain as a Marker of Progression in Parkinson's Disease: Long-Term Observation and Implications of Clinical Subtypes

J Parkinsons Dis. 2022;12(2):571-584. doi: 10.3233/JPD-212866.


Background: Biochemical and clinical biomarkers correlate with progression rate and disease severity in Parkinson's disease (PD) but are not sufficiently studied in late PD.

Objective: To examine how serum neurofilament light chain (S-NfL) alone or combined with clinical classifications predicts PD outcome in later disease stages.

Methods: Eighty-five patients with 7.9±5.1 years of PD duration were included in an observational cohort. Clinical scores were obtained at two separate examinations 8.2±2.0 years apart. S-NfL levels were determined with single molecule array (SiMoA). Five predefined disease progression milestones were assessed. After affirming combination potential of S-NfL and either of two clinical classifications, three combined models were constructed based on these factors and age at onset in different combinations.

Results: S-NfL levels showed significant hazard ratios for four out of five disease progression milestones: walking-aid usage (HR 3.5; 95% CI 1.4-8.5), nursing home living (5.1; 2.1-12.5), motor end-stage (6.2; 2.1-17.8), and death (4.1; 1.7-9.7). Higher S-NfL levels were associated with lower ability in activities of daily living and poorer cognition at baseline and/or at follow-up. Combined models showed significantly improved area under receiver operating characteristic curves (0.77-0.91) compared to S-NfL levels alone (0.68-0.71) for predicting the five disease milestones.

Conclusion: S-NfL levels stratified patients according to their likelihood to reach clinically relevant progression milestones during this long-term observational study. S-NfL alone reflected motor and social outcomes in later stages of PD. Combining S-NfL with clinical factors was possible and exploratory combined models improved prognostic accuracy.

Keywords: Parkinson’s disease; biomarkers; dementia; mortality; neurofilament proteins; prognosis.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Biomarkers
  • Disease Progression
  • Humans
  • Intermediate Filaments
  • Neurofilament Proteins
  • Parkinson Disease* / complications


  • Biomarkers
  • Neurofilament Proteins