Journal
STROKE
Volume 52, Issue 3, Pages 896-904Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.120.030302
Keywords
biomarkers; cerebral small vessel diseases; magnetic resonance imaging; plasma; stroke; lacunar; white matter
Categories
Funding
- National Natural Science Foundation of China [91849126, 81571245, 81771148]
- National Key R&D Program of China [2018YFC1314700]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]
- ZHANGJIANG LAB
- Alzheimer disease neuroimaging initiative (ADNI
- National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense ) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer Association
- Alzheimer Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc
- Cogstate
- Eisai Inc
- Elan Pharmaceuticals, Inc
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Fujirebio
- GE Healthcare
- IXICO Ltd
- Janssen Alzheimer Immunotherapy Research & Development, LLC
- Johnson & Johnson Pharmaceutical Research & Development LLC
- Lumosity
- Lundbeck
- Merck Co, Inc
- Meso Scale Diagnostics, LLC
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Tianqiao and Chrissy Chen Institute
- State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University
- Genentech, Inc
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The study found that plasma NfL levels can serve as an effective marker for monitoring the progression of cerebral small vessel disease (CSVD) among nondemented individuals. Higher NfL levels were associated with greater CSVD burden, and dynamic increases in NfL levels may predict a more significant progression of CSVD.
Background and Purpose: Neurofilament light chain (NfL) is a promising predictive biomarker of active axonal injury and neuronal degeneration diseases. We aimed to evaluate if an increase in plasma NfL levels could play a monitoring role in the progression of cerebral small vessel disease (CSVD) among the nondemented elders, which are highly prevalent in elderly individuals and associated with an increased risk of stroke and dementia. Methods: The study included 496 nondemented participants from the Alzheimer disease neuroimaging initiative database. All participants underwent plasma NfL measurements and 3.0-Tesla magnetic resonance imaging of the brain; 387 (78.0%) underwent longitudinal measurements. The number of cerebral microbleeds, lacunar infarcts, and volumetric white matter hyperintensities, as well as Fazekas scores, were measured. Cross-sectional and longitudinal associations between CSVD burden and NfL levels were evaluated using multivariable-adjusted models. Results: Plasma NfL was higher in the moderate-severe CSVD burden group (45.2 +/- 16.0 pg/mL) than in the nonburden group (34.3 +/- 15.1 pg/mL; odds ratio [OR]=1.71 [95% CI, 1.24-2.35]) at baseline. NfL was positively associated with the presence of cerebral microbleeds (OR=1.29 [95% CI, 1.01-1.64]), lacunar infarcts (OR=1.43 [95% CI, 1.06-1.93]), and moderate-severe white matter hyperintensities (OR=1.67 [95% CI, 1.24-2.25]). Longitudinally, a higher change rate of NfL could predict more progression of CSVD burden (OR=1.38 [95% CI, 1.08-1.76]), white matter hyperintensities (OR=1.41 [95% CI, 1.10-1.79]), and lacunar infarcts (OR=1.99 [95% CI, 1.42-2.77]). Conclusions: Plasma NfL level is a valuable noninvasive biomarker that supplements magnetic resonance imaging scans and possibly reflects the severity of CSVD burden. Furthermore, high plasma NfL levels tend to represent an increased CSVD risk, and dynamic increases in NfL levels might predict a greater progression of CSVD.
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