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

Neurofilament relates to white matter microstructure in older adults

Elizabeth E Moore  1 , Timothy J Hohman  1 , Faizan S Badami  1 , Kimberly R Pechman  1 , Katie E Osborn  1 , Lealani Mae Y Acosta  1 , Susan P Bell  2 , Michelle A Babicz  3 , Katherine A Gifford  1 , Adam W Anderson  4 , Lee E Goldstein  5 , Kaj Blennow  6 , Henrik Zetterberg  7 , Angela L Jefferson  8
Affiliations

Neurofilament relates to white matter microstructure in older adults

Elizabeth E Moore et al. Neurobiol Aging. 2018 Oct.

Abstract

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.

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Conflict of interest statement

Declarations of Interest

None

Figures

Figure 1
Figure 1. Participant Inclusion/Exclusion Details
Missing data categories are mutually exclusive. Of the 6 participants excluded for missing NFL data, 1 was defined as an outlier. CSF=cerebrospinal fluid; DTI=diffusion tensor imaging; MCI=mild cognitive impairment; NC=normal cognition; NFL=neurofilament l ight; T-tau=total tau.
Figure 2
Figure 2. NFL & DTI Results
Panel A: Association between NFL and fractional anisotropy. Mean FA skeleton shows regions where NFL is associated with FA. Scatterplot shows least squares regression relating mean FA values for every participant at one specific cluster and NFL levels. Panel B: Association between NFL and diffusivity metrics. Mean FA skeletons show regions where NFL is associated with mean, radial, and axial diffusivity. Parametric p-values, β, and region listed only represent the cluster with the lowest p-value for each DTI metric. All skeleton images taken at Z=91. DTI=diffusion tensor imaging; FA=fractional anisotropy; NFL=neurofilament light.
Figure 3
Figure 3. NFL & Fractional Anisotropy by Diagnosis, Amyloid Status, & T-Tau Status
Mean FA skeletons show regions where NFL is associated with FA in models stratified by cognitive diagnosis, amyloid status, and t-tau status. Significance is seen in MCI, amyloid negative, and t-tau positive only. All skeleton images taken at Z=91. DTI=diffusion tensor imaging; MCI=mild cognitive impairment; NC=normal cognition; NFL=neurofilament light; T-tau=total tau.
See this image and copyright information in PMC

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