1. Cerebrospinal fluid α-synuclein predicts neurodegeneration and clinical progression in non-demented elders.
- Author
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Li JQ, Bi YL, Shen XN, Wang HF, Xu W, Tan CC, Dong Q, Wang YJ, Tan L, and Yu JT
- Subjects
- Aged, Aged, 80 and over, Biomarkers cerebrospinal fluid, China epidemiology, Cohort Studies, Female, Humans, Male, Middle Aged, Neurodegenerative Diseases epidemiology, Predictive Value of Tests, Dementia, Disease Progression, Neurodegenerative Diseases cerebrospinal fluid, Neurodegenerative Diseases diagnostic imaging, alpha-Synuclein cerebrospinal fluid
- Abstract
Background: Accumulating reports have suggested that α-synuclein is involved in the pathogenesis of Alzheimer's disease (AD). As the cerebrospinal fluid (CSF) α-synuclein has been suggested as a potential biomarker of AD, this study was set out to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented elders., Methods: The associations between CSF α-synuclein and other AD biomarkers were investigated at baseline in non-demented Chinese elders. The predictive values of CSF α-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 α-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 α-synuclein concentrations were found to increase with disease severity. The CSF α-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 α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia., Conclusions: CSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented elders. This finding indicates that CSF α-synuclein is a potentially useful early biomarker for AD.
- Published
- 2020
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