Brain atrophy and white matter hyperintensities are independently associated with plasma neurofilament light chain in an Asian cohort of patients with mixed pathology

BACKGROUND AND OBJECTIVES:Neurofilament light chain (NfL) in blood is a sensitive but non-specific marker of brain injury. This study sought to evaluate associations between NfL concentration and MRI findings of vascular brain injury in older adults.METHODS:A longitudinal cohort study included two cranial MRI scans performed about 5 years apart and assessed for white matter hyperintensities (WMH) and infarcts. About one year before their second MRI, 1,362 participants (median age 77 years and 61.4% women) without a history of TIA or stroke had measurement of four biomarkers: NfL, total tau, glial fibrillary acidic protein (GFAP), and ubiquitin carboxyl-terminal hydrolase L1. Most (n = 1,279) also had the first MRI scan, and some (n=633) had quantitative measurements of hippocampal and WMH. In primary analyses, we assessed associations of NfL with a 10-point white matter grade (WMG) and prevalent infarcts on second MRI and with worsening WMG and incident infarct comparing the two scans. A p-value <0.0125 (0.05/4) was considered significant for these analyses. We also assessed associations with hippocampal and WMH volume.RESULTS:In fully adjusted models, log2(NfL) concentration was associated with WMG (β=0.27; p=2.3x10-4) and worsening WMG (RR=1.24; p=0.0022), but less strongly with prevalent brain infarcts (RR=1.18; p=0.013) and not with incident brain infarcts (RR=1.18; p=0.18). Associations were also present with WMH volume (beta=2242.9, p=0.0036). For the other three biomarkers, the associations for log2(GFAP) concentration with WMG and worsening WMG were significant.DISCUSSION:Among older adults without a history of stroke, higher serum NfL concentration was associated with covert MRI findings of vascular brain injury, especially the burden of WMH and its worsening. Whether these results offer opportunities for the use of NfL as a non-invasive biomarker of WMH or to control vascular risk factors remains to be determined.

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Associations between neurofilament light chain levels, disease activity and brain atrophy in progressive multiple sclerosis

Biomedical Papers ◽

10.5507/bp.2021.034 ◽

2021 ◽

Author(s):

Jarmila Szilasiova ◽

Pavol Mikula ◽

Jaroslav Rosenberger ◽

Miriam Fedicova ◽

Peter Urban ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Light Chain ◽

Brain Atrophy ◽

Progressive Multiple Sclerosis ◽

Neurofilament Light Chain ◽

Neurofilament Light

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Serum neurofilament light chain in behavioral variant frontotemporal dementia

Neurology ◽

10.1212/wnl.0000000000006318 ◽

2018 ◽

Vol 91 (15) ◽

pp. e1390-e1401 ◽

Cited By ~ 27

Author(s):

Petra Steinacker ◽

Sarah Anderl-Straub ◽

Janine Diehl-Schmid ◽

Elisa Semler ◽

Ingo Uttner ◽

...

Keyword(s):

Frontotemporal Dementia ◽

Light Chain ◽

Brain Atrophy ◽

Rating Scale ◽

Neurofilament Light Chain ◽

Behavioral Variant Frontotemporal Dementia ◽

Neurofilament Light ◽

Baseline Serum ◽

Functional Scores

ObjectiveTo determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD).MethodsBlood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration–related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry.ResultsAt baseline, serum NfL level correlated with CSF NfL (bvFTDr= 0.706,p< 0.0001; AD/MCIr= 0.666,p= 0.0003). Highest serum levels were observed in bvFTD (p<0 0.0001 vs Con and MCI,p= 0.0078 vs AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with 91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL increased in bvFTD and AD (p= 0.0039 andp= 0.0006, respectively). At baseline and follow-up, NfL correlated with functional scores of patients with bvFTD (e.g., CDR-SOB [baseline]r= 0.4157,p= 0.0006; [follow-up]r= 0.5629,p< 0.0001) and with atrophy in the gray and white matter of many brain regions including frontal and subcortical areas (e.g., frontal lobe:r= −0.5857,p< 0.0001; 95% confidence interval −0.7415 to −0.3701). For patients with AD/MCI, NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline]r= 0.6624,p< 0.0001; [follow-up]r= 0.5659,p= 0.0003) but not with regional brain volumes.ConclusionsAs serum NfL correlates with functional impairment and brain atrophy in bvFTD at different disease stages, we propose it as marker of disease severity, paving the way for its future use as outcome measure for clinical trials.Classification of evidenceThis study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia.

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