Neurofilament relates to white matter microstructure in older adults

Neurobiol Aging. 2018 Oct;70:233-241. doi: 10.1016/j.neurobiolaging.2018.06.023. Epub 2018 Jun 28.


Cerebrospinal fluid (CSF) neurofilament light (NFL) is a protein biomarker of axonal injury. To study whether NFL is associated with diffusion tensor imaging (DTI) measurements of white matter (WM) microstructure, Vanderbilt Memory & Aging Project participants with normal cognition (n = 77), early mild cognitive impairment (n = 15), and MCI (n = 55) underwent lumbar puncture to obtain CSF and 3T brain MRI. Voxel-wise analyses cross-sectionally related NFL to DTI metrics, adjusting for demographic and vascular risk factors. Increased NFL correlated with multiple DTI metrics (p-values < 0.05). An NFL × diagnosis interaction (excluding early mild cognitive impairment) on WM microstructure (p-values < 0.05) was detected, with associations strongest among MCI. Multiple NFL × CSF biomarker interactions were detected. Associations between NFL and worse WM metrics were strongest among amyloid-β42-negative, tau-positive, and suspected nonamyloid pathology participants. Findings suggest increased NFL, a biomarker of axonal injury, is correlated with compromised WM microstructure. Results highlight the role of elevated NFL in predicting WM damage in cognitively impaired older adults who are amyloid-negative, tau-positive, or meet suspected nonamyloid pathology criteria.

Keywords: Alzheimer's disease; Cerebrospinal fluid; Diffusion tensor imaging; Neurofilament light.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / cerebrospinal fluid
  • Aging / physiology*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Brain / anatomy & histology
  • Brain / diagnostic imaging*
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnostic imaging*
  • Cohort Studies
  • Diffusion Tensor Imaging
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neurofilament Proteins / cerebrospinal fluid*
  • Peptide Fragments / cerebrospinal fluid
  • White Matter / anatomy & histology
  • White Matter / diagnostic imaging*


  • Amyloid beta-Peptides
  • Biomarkers
  • Neurofilament Proteins
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • neurofilament protein L