Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases

Neuron. 2016 Jul 6;91(1):56-66. doi: 10.1016/j.neuron.2016.05.018. Epub 2016 Jun 9.


A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (α-synuclein, Tau, Aβ). To monitor such treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of α-synucleinopathies, tauopathy, and β-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of α-synuclein lesions increased CSF and blood NfL levels, while blocking Aβ lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human α-synucleinopathies, tauopathies, and Alzheimer's disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progression and treatment response in mouse models and potentially in human proteopathic neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Brain / metabolism
  • Brain / pathology
  • Disease Progression
  • Intermediate Filaments / metabolism*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurodegenerative Diseases / diagnosis
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Neurofilament Proteins / blood*
  • Neurofilament Proteins / cerebrospinal fluid*
  • alpha-Synuclein / metabolism


  • Biomarkers
  • Neurofilament Proteins
  • alpha-Synuclein