Journal
AGING-US
Volume 11, Issue 13, Pages 4521-4535Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.102066
Keywords
genome-wide association study; plasma NFL; non-demented elders; CD1A; genetic factors
Categories
Funding
- National Natural Science Foundation of China [91849126]
- National Key R&D Program of China [2018YFC1314700]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]
- ZHANGJIANG LAB
- Tianqiao and Chrissy Chen Institute
- Frontiers Center for Brain Science of Ministry of Education, Fudan University
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense award) [W81XWH-12-2-0012]
- National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's 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
- Genentech, Inc.
- 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
- State Key Laboratory of Neurobiology of Ministry of Education, Fudan University
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As a marker of neuroaxonal injury, neurofilament light (NFL) in blood is robustly elevated in many neurodegenerative conditions. We aimed to discover single nucleotide polymorphisms (SNPs) associated with longitudinal changes in plasma NFL levels that affect the risk of developing neurodegenerative disease and clinical disease progression. 545 eligible non-Hispanic white participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with longitudinal plasma NFL data were included. Three SNPs (rs16840041, p=4.50x10(-8); rs2269714, p=4.50x10(-8); rs2269715, p=4.83x10(-8)) in CD1A were in high linkage disequilibrium (LD) and significantly associated with the increase in plasma NFL levels. We demonstrate a promoting effect of rs16840041-A on clinical disease progression (p = 0.006). Moreover, the minor allele (A) of rs16840041 was significantly associated with accelerated decline in [F-18] Fluorodeoxyglucose (FDG) (estimate -1.6% per year [95% CI -0.6 to -2.6], p=0.0024). CD1A is a gene involved in longitudinal changes in plasma NFL levels and AD-related phenotypes among non-demented elders. Given the potential effects of these variants, CD1A should be further investigated as a gene of interest in neurodegenerative diseases and as a potential target for monitoring disease trajectories and treating disease.
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