Tau forms in CSF as a reliable biomarker for progressive supranuclear palsy
Tau forms in CSF as a reliable biomarker for progressive supranuclear palsy
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DOI：
10.1212/01.wnl.0000335941.68602.39
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发表时间：
2008-11-25
期刊：
影响因子：
9.9
通讯作者：
Padovani, A.
中科院分区：
文献类型：
--
作者：
Borroni, B.;Malinverno, M.;Padovani, A.
目的：在脑脊液中，已发现有延长的(55 KDa)和截短的(33 KDa)tau形式，进行性核上性瘫痪(PSP)的tau 33 kDa/55 kDa比在其他神经退行性疾病中显著降低。本研究的目的是评价脑脊液tau形态比作为PSP生物标志物的诊断价值以及体素形态计量学(VBM)测量的脑脊液tau形态比下降与脑脊液tau形态比下降的相关性。方法：166例受试者包括21例PSP、20例皮质基底膜变性综合征、44例额颞叶痴呆、29例阿尔茨海默病、10例帕金森病、15例路易体痴呆和27例非神经退行性疾病患者。每个患者都接受了标准化的临床和神经心理评估。在脑脊液中，用半定量免疫沉淀法测定脑脊液tau蛋白33 kDa/55 kDa的比值。结果：与年龄匹配的对照组(0.989+/-0.343)和其他神经退行性疾病患者(范围0.899-1.215)相比，PSP患者的tau形态比率(0.504+/-0.284)显著降低。受试者工作特性分析的曲线下面积(AUC)范围为0.863~0.937(PSP与其他亚组比较，AUC=0.897，p<；0.0001)。VBM研究显示脑脊液tau形态比下降与脑干萎缩显著相关。结论：截短tau产物选择性地影响脑干神经元敏感性，可作为PSP的特异性和可靠性指标。在进行性核上性麻痹中，tau形式的比例最低，与任何其他神经退行性疾病没有重叠。神经病学(R)2008；71：1796-1803
Objective: In CSF, extended (55 kDa) and truncated (33 kDa) tau forms have been previously recognized, and the tau 33 kDa/55 kDa ratio has been found significantly reduced in progressive supranuclear palsy (PSP) vs in other neurodegenerative disorders. The aim of this study was to evaluate the diagnostic value of the CSF tau form ratio as a biomarker of PSP and to correlate the structural anatomic changes as measured by means of voxel-based morphometry (VBM) to CSF tau form ratio decrease.Methods: A total of 166 subjects were included in the study (21 PSP, 20 corticobasal degeneration syndrome, 44 frontotemporal dementia, 29 Alzheimer disease, 10 Parkinson disease, 15 dementia with Lewy bodies, and 27 individuals without any neurodegenerative disorder). Each patient underwent a standardized clinical and neuropsychological evaluation. In CSF, a semiquantitative immunoprecipitation was developed to evaluate CSF tau 33 kDa/55 kDa ratio. MRI assessment and VBM analysis was carried out.Results: Tau form ratio was significantly reduced in patients with PSP (0.504 +/- 0.284) when compared to age-matched controls (0.989 +/- 0.343), and to patients with other neurodegenerative conditions (range = 0.899-1.215). The area under the curve (AUC) of the receiver operating characteristic analysis in PSP vs other subgroups ranged from 0.863 to 0.937 (PSP vs others, AUC = 0.897, p < 0.0001). VBM study showed that CSF tau form ratio decrease correlated significantly with brainstem atrophy.Conclusions: Truncated tau production, which selectively affects brainstem neuron susceptibility, can be considered a specific and reliable marker for PSP. Tau form ratio was the lowest in progressive supranuclear palsy with no overlap with any other neurodegenerative illness. Neurology (R) 2008; 71:1796-1803