Comparison of CSF neurofilament light chain, neurogranin, and tau to MRI markers

Michelle M. Mielke, Scott A. Przybelski, Timothy G. Lesnick, Silke Kern, Henrik Zetterberg, Kaj Blennow, David S. Knopman, Jonathan Graff-Radford, Ronald C. Petersen, Clifford R. Jack, Prashanthi Vemuri

Research output: Contribution to journalArticlepeer-review


Introduction: We determined whether cerebrospinal fluid (CSF) neurofilament light (NfL), neurogranin (Ng), and total-tau (t-tau) differentially mapped to magnetic resonance imaging (MRI) measures of cortical thickness, microstructural integrity (corpus callosum and cingulum fractional anisotropy [FA]), and white matter hyperintensities (WMH). Methods: Analyses included 536 non-demented Mayo Clinic Study of Aging participants with CSF NfL, Ng, t-tau, amyloid beta (Aβ)42 and longitudinal MRI scans. Linear mixed models assessed longitudinal associations between CSF markers and MRI changes. Results: Higher CSF NfL was associated with decreasing microstructural integrity and WMH. Higher t-tau was associated with decreasing temporal lobe and Alzheimer's disease (AD) meta region of interest (ROI) cortical thickness. There was no association between Ng and any MRI measure. CSF Aβ42 interacted with Ng for declines in temporal lobe and AD meta ROI cortical thickness and cingulum FA. Discussion: CSF NfL predicts changes in white matter integrity, t-tau reflects non-specific changes in cortical thickness, and Ng reflects AD-specific synaptic and neuronal degeneration.

Original languageEnglish (US)
Pages (from-to)801-812
Number of pages12
JournalAlzheimer's and Dementia
Issue number5
StatePublished - May 2021


  • Alzheimer's
  • amyloid
  • cerebrospinal fluid
  • cohort study
  • cortical thickness
  • magnetic resonance imaging
  • neurodegeneration
  • neurofilament light chain
  • neurogranin
  • total tau
  • white matter integrity

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health


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