Cerebrospinal fluid α-synuclein predicts neurodegeneration and clinical progression in non-demented elders.

Publisher: BioMed Central Country of Publication: England NLM ID: 101591861 Publication Model: Electronic Cited Medium: Print ISSN: 2047-9158 (Print) Linking ISSN: 20479158 NLM ISO Abbreviation: Transl Neurodegener Subsets: MEDLINE

Original Publication: [London] : BioMed Central, 2012-

Dementia* ; Disease Progression*; Neurodegenerative Diseases/*cerebrospinal fluid ; Neurodegenerative Diseases/*diagnostic imaging ; alpha-Synuclein/*cerebrospinal fluid; Aged ; Aged, 80 and over ; Biomarkers/cerebrospinal fluid ; China/epidemiology ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Neurodegenerative Diseases/epidemiology ; Predictive Value of Tests

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.

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91849126 International National Natural Science Foundation of China; 2018YFC1314700 International National Key R&D Program of China; 2018SHZDZX01 International Shanghai Municipal Science and Technology Major Project

Keywords: Alzheimer’s disease; Biomarker; Cerebrospinal fluid; Neurodegeneration; α-Synuclein

0 (Biomarkers)
0 (alpha-Synuclein)

Date Created: 20201124 Date Completed: 20210930 Latest Revision: 20210930

20231215

PMC7685645

10.1186/s40035-020-00222-1

33228804