Cerebrospinal Fluid Tau/α-Synuclein Ratio in Parkinson's Disease and Degenerative Dementias
Cerebrospinal Fluid Tau/α-Synuclein Ratio in Parkinson's Disease and Degenerative Dementias
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DOI：
10.1002/mds.23670
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发表时间：
2011-07-01
影响因子：
8.6
通讯作者：
El-Agnaf, Omar
中科院分区：
文献类型：
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作者：
Parnetti, Lucilla;Chiasserini, Davide;El-Agnaf, Omar
虽然α-突触核蛋白是路易体的主要成分，但脑脊液测定本身似乎对突触核蛋白病的诊断并不重要。我们评估了经典生物标志物A β（1-42）、总tau蛋白、磷酸化tau蛋白和α-突触核蛋白的组合是否可以提高对帕金森病、路易体痴呆、阿尔茨海默病和额颞叶痴呆的区分。在一系列患有帕金森病（n = 38）、路易体痴呆（n = 32）、阿尔茨海默病（n = 48）、额颞叶痴呆（n = 31）和年龄匹配的患有其他神经系统疾病的对照患者（n = 32）中测量A β（1-42）、总tau、磷酸化tau和α-突触核蛋白。病理组的脑脊液中平均α-突触核蛋白水平显著低于认知健康受试者。观察到α-突触核蛋白与总tau的负相关（r =-0.196，P <0.01）。在帕金森病患者组中，A β（1-42）、总tau和磷酸化tau值与对照组相似，而总tau/α-突触核蛋白和磷酸化tau/α-突触核蛋白比值显示最低值。单独的脑脊液α-突触核蛋白不能为帕金森病的诊断提供相关信息，显示出较低的特异性（曲线下面积，0.662;灵敏度，94%;特异性，25%）。相反，使用总tau/α-syn比率获得了更好的性能（曲线下面积，0.765;灵敏度，89%;特异性，61%）。脑脊液中α-突触核蛋白和经典生物标志物的联合测定显示了神经退行性疾病的差异模式。特别地，总tau/α-突触核蛋白和磷酸化tau/α-突触核蛋白比率可以有助于区分帕金森病。(C)2011年运动障碍学会
Although alpha-synuclein is the main constituent of Lewy bodies, cerebrospinal fluid determination on its own does not seem fundamental for the diagnosis of synucleinopathies. We evaluated whether the combination of classical biomarkers, A beta(1-42), total tau, phosphorylated tau, and alpha-synuclein can improve discrimination of Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, and frontotemporal dementia. A beta(1-42), total tau, phosphorylated tau, and alpha-synuclein were measured in a series of patients with Parkinson's disease (n = 38), dementia with Lewy bodies (n = 32), Alzheimer's disease (n = 48), frontotemporal dementia (n = 31), and age-matched control patients with other neurological diseases (n = 32). Mean alpha-synuclein levels in cerebrospinal fluid were significantly lower in the pathological groups than in cognitively healthy subjects. An inverse correlation of alpha-synuclein with total tau (r = -0.196, P < .01) was observed. In the group of patients with Parkinson's disease, A beta(1-42), total tau, and phosphorylated tau values were similar to controls, whereas total tau/alpha-synuclein and phosphorylated tau/alpha-synuclein ratios showed the lowest values. Cerebrospinal fluid alpha-synuclein alone did not provide relevant information for Parkinson's disease diagnosis, showing low specificity (area under the curve, 0.662; sensitivity, 94%; specificity, 25%). Instead, a better performance was obtained with the total tau/alpha-syn ratio (area under the curve, 0.765; sensitivity, 89%; specificity, 61%). Combined determination of alpha-synuclein and classical biomarkers in cerebrospinal fluid shows differential patterns in neurodegenerative disorders. In particular, total tau/alpha-synuclein and phosphorylated tau/alpha-synuclein ratios can contribute to the discrimination of Parkinson's disease. (C) 2011 Movement Disorder Society