J Stroke.
2018 May;20(2):228-238. 10.5853/jos.2017.02565.
Serum Neurofilament Light Chain Levels Are Related to Small Vessel Disease Burden
- Affiliations
-
- 1Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany. marco.duering@med.uni-muenchen.de
- 2Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
- 3Stroke Center and Department of Neurology, University Hospital Basel, Basel, Switzerland.
- 4Neurorehabilitation Unit, University of Basel and University Center for Medicine of Aging, Felix Platter Hospital, Basel, Switzerland.
- 5Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital of Basel, Basel, Switzerland.
- 6Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
- KMID: 2424426
- DOI: http://doi.org/10.5853/jos.2017.02565
Abstract
- BACKGROUND AND PURPOSE
Neurofilament light chain (NfL) is a blood marker for neuroaxonal damage. We assessed the association between serum NfL and cerebral small vessel disease (SVD), which is highly prevalent in elderly individuals and a major cause of stroke and vascular cognitive impairment.
METHODS
Using a cross-sectional design, we studied 53 and 439 patients with genetically defined SVD (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy [CADASIL]) and sporadic SVD, respectively, as well as 93 healthy controls. Serum NfL was measured by an ultrasensitive single-molecule array assay. We quantified magnetic resonance imaging (MRI) markers of SVD, i.e., white matter hyperintensity volume, lacune volume, brain volume, microbleed count, and mean diffusivity obtained from diffusion tensor imaging. Clinical characterization included neuropsychological testing in both SVD samples. CADASIL patients were further characterized for focal neurological deficits (National Institutes of Health stroke scale [NIHSS]) and disability (modified Rankin scale [mRS]).
RESULTS
Serum NfL levels were elevated in both SVD samples (P < 1e-05 compared with controls) and associated with all SVD MRI markers. The strongest association was found for mean diffusivity (CADASIL, R2=0.52, P=1.2e-09; sporadic SVD, R2=0.21, P < 1e-15). Serum NfL levels were independently related to processing speed performance (CADASIL, R2=0.27, P=7.6e-05; sporadic SVD, R2=0.06, P=4.8e-08), focal neurological symptoms (CADASIL, NIHSS, P=4.2e-05) and disability (CADASIL, mRS, P=3.0e-06).
CONCLUSIONS
We found serum NfL levels to be associated with both imaging and clinical features of SVD. Serum NfL might complement MRI markers in assessing SVD burden. Importantly, SVD needs to be considered when interpreting serum NfL levels in the context of other age-related diseases.
Keyword
MeSH Terms
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Academies and Institutes
Aged
Biomarkers
Brain
CADASIL
Cerebral Small Vessel Diseases
Cognition Disorders
Complement System Proteins
Dementia, Vascular
Diffusion Tensor Imaging
Humans
Intermediate Filaments*
Leukoencephalopathies
Magnetic Resonance Imaging
Neuropsychological Tests
Stroke
White Matter
Biomarkers
Complement System Proteins
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