期刊
TRANSLATIONAL NEURODEGENERATION
卷 9, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s40035-020-00222-1
关键词
Alzheimer's disease; alpha-Synuclein; Biomarker; Cerebrospinal fluid; Neurodegeneration
资金
- National Natural Science Foundation of China [91849126]
- National Key R&D Program of China [2018YFC1314700]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]
- State Key Laboratory of Neurobiology and 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) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Cogstate
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- Fujirebio
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Merck Co., Inc.
- Meso Scale Diagnostics
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- ADNI clinical sites in Canada
- Foundation for the National Institutes of Health
- Northern California Institute for Research and Education
- Laboratory for Neuro Imaging at the University of Southern California
Background: Accumulating reports have suggested that alpha-synuclein is involved in the pathogenesis of Alzheimer's disease (AD). As the cerebrospinal fluid (CSF) alpha-synuclein has been suggested as a potential biomarker of AD, this study was set out to test whether CSF alpha-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented elders. Methods: The associations between CSF alpha-synuclein and other AD biomarkers were investigated at baseline in non-demented Chinese elders. The predictive values of CSF alpha-synuclein for longitudinal neuroimaging change and the conversion risk of non-demented elders were assessed using linear mixed effects models and multivariate Cox proportional hazard models, respectively, in the Alzheimer's disease Neuroimaging Initiative (ADNI) database. Results: The CSF alpha-synuclein levels correlated with AD-specific biomarkers, CSF total tau and phosphorylated tau levels, in 651 Chinese Han participants (training set). These positive correlations were replicated in the ADNI database (validation set). Using a longitudinal cohort from ADNI, the CSF alpha-synuclein concentrations were found to increase with disease severity. The CSF alpha-synuclein had high diagnostic accuracy for AD based on the ATN (amyloid, tau, neurodegeneration) system (A + T+ versus A - T - control) (area under the receiver operating characteristic curve, 0.84). Moreover, CSF alpha-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia. Conclusions: CSF alpha-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented elders. This finding indicates that CSF alpha-synuclein is a potentially useful early biomarker for AD.
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