Department of Pathology, University of Washington School of Medicine, Seattle, WA 98104, USA.
J Alzheimers Dis. 2013;36(4):679-88. doi: 10.3233/JAD-130458.
In addition to amyloid-β (Aβ) and tau, α-synuclein, best known for its role in Parkinson's disease (PD), has been suggested to be involved in cognition and pathogenesis of Alzheimer's disease (AD). We investigate the potential of α-synuclein in cerebrospinal fluid (CSF) as a biomarker of cognitive decline in AD, and its prodromal phase, mild cognitive impairment (MCI). Using an established, sensitive Luminex assay, we measured α-synuclein levels in the CSF of a cohort of close to 400 healthy control, MCI, and AD subjects obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and factored in APOE genotype in data analysis. CSF α-synuclein levels were significantly higher in the MCI (p = 0.005) and AD (p < 0.001) groups, compared to controls. However, receiver operating characteristic (ROC) curve analysis suggests that CSF α-synuclein level on its own only offered modest sensitivity (65%) and specificity (74%) as a diagnostic marker of AD, with an area under the curve (AUC) value of 0.719 for AD versus controls. The effect of APOE genotype, if any, was quite subtle. However, there was a significant correlation between α-synuclein and cognition (p = 0.001), with increased α-synuclein levels associated with decreased Mini-Mental State Exam scores. Our results support a role for α-synuclein even in MCI, the early phase of AD, in addition to being a potential contributor in MCI and AD diagnosis or monitoring of disease progression.
除了淀粉样蛋白-β（Aβ）和 tau 外，α-突触核蛋白也因在帕金森病（PD）中的作用而广为人知，它被认为与阿尔茨海默病（AD）的认知和发病机制有关。我们研究了α-突触核蛋白在脑脊液（CSF）中作为 AD 认知下降的生物标志物的潜力，以及其前驱期轻度认知障碍（MCI）。使用一种已建立的、敏感的 Luminex 检测法，我们测量了接近 400 名健康对照、MCI 和 AD 受试者的 CSF 中α-突触核蛋白的水平，这些受试者来自阿尔茨海默病神经影像学倡议（ADNI），并在数据分析中考虑了 APOE 基因型。与对照组相比，MCI（p = 0.005）和 AD 组（p < 0.001）的 CSF α-突触核蛋白水平显著升高。然而，接受者操作特征（ROC）曲线分析表明，CSF α-突触核蛋白水平本身作为 AD 的诊断标志物仅提供了适度的敏感性（65%）和特异性（74%），其对 AD 与对照组的曲线下面积（AUC）值为 0.719。APOE 基因型的影响如果有的话，相当微妙。然而，α-突触核蛋白与认知之间存在显著相关性（p = 0.001），α-突触核蛋白水平升高与 Mini-Mental State 检查分数降低有关。我们的结果支持 α-突触核蛋白在 MCI 中的作用，MCI 是 AD 的早期阶段，此外，它还是 MCI 和 AD 诊断或监测疾病进展的潜在贡献者。
