Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 20040, China.
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, China.
Transl Neurodegener. 2020 Nov 23;9(1):41. doi: 10.1186/s40035-020-00222-1.
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.
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.
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.
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.
越来越多的报告表明α-突触核蛋白参与了阿尔茨海默病（AD）的发病机制。由于脑脊液（CSF）α-突触核蛋白被认为是 AD 的潜在生物标志物，因此本研究旨在检验 CSF α-突触核蛋白是否与其他 AD 生物标志物相关，以及是否可以预测无痴呆老年人的神经退行性变和临床进展。
在非痴呆的中国老年人中，在基线时研究了 CSF α-突触核蛋白与其他 AD 生物标志物之间的相关性。在阿尔茨海默病神经影像学倡议（ADNI）数据库中，使用线性混合效应模型和多变量 Cox 比例风险模型分别评估了 CSF α-突触核蛋白对纵向神经影像学变化和无痴呆老年人的转换风险的预测值。
在 651 名中国汉族参与者（训练集）中，CSF α-突触核蛋白水平与 AD 特异性生物标志物 CSF 总 tau 和磷酸化 tau 水平相关。这些正相关在 ADNI 数据库中得到了复制（验证集）。使用 ADNI 的纵向队列，发现 CSF α-突触核蛋白浓度随疾病严重程度而增加。基于“ATN”（淀粉样蛋白、tau、神经退行性变）系统（A+T+与 A-T-对照），CSF α-突触核蛋白对 AD 具有较高的诊断准确性（接受者操作特征曲线下面积，0.84）。此外，CSF α-突触核蛋白预测了从 MCI 向 AD 痴呆的纵向海马萎缩和转化。
CSF α-突触核蛋白与 CSF tau 水平相关，并可预测无痴呆老年人的神经退行性变和临床进展。这一发现表明 CSF α-突触核蛋白是 AD 的一种潜在有用的早期生物标志物。
