Borroni B, Gardoni F, Parnetti L, Magno L, Malinverno M, Saggese E, Calabresi P, Spillantini M G, Padovani A, Di Luca M
Department of Neurology, University of Brescia, Italy.
Neurobiol Aging. 2009 Jan;30(1):34-40. doi: 10.1016/j.neurobiolaging.2007.05.009. Epub 2007 Aug 20.
Cerebrospinal fluid (CSF) total Tau levels vary widely in neurodegenerative disorders, thus being not useful in their discrimination over Alzheimer disease. No CSF marker for progressive supranuclear palsy (PSP) is currently available. The aim of this study was to characterise and measure Tau forms in order to verify the differential patterns among neurodegenerative disorders. Seventy-eight patients with neurodegenerative disorders and 26 controls were included in the study. Each patient underwent a standardised clinical and neuropsychological evaluation, MRI, and CSF total-Tau and phospho-Tau dosage. In CSF and cerebral cortex, a quantitative immunoprecipitation was developed. An extended (55 kDa), and a truncated (33 kDa) forms of Tau were recognised. CSF samples were assayed, the optical density of the two Tau forms was measured, and the ratio calculated (Tau ratio, 33 kDa/55 kDa forms). Tau ratio 33 kDa/55 kDa was significantly decreased in patients with PSP (0.46+/-0.16) when compared to controls, including healthy subjects (1.16+/-0.46, P=0.002) and Alzheimer disease (1.38+/-0.68, P<0.001), and when compared to frontotemporal dementia (0.98+/-0.30, P=0.008) or corticobasal degeneration syndrome (0.98+/-0.48, P=0.02). Moreover, in PSP patients Tau form ratio was lower than in other neurodegenerative extrapyramidal disorders, such as Parkinson disease (1.16+/-0.26, P=0.002) and dementia with lewy bodies (1.44+/-0.48, P<0.001). Tau ratio 33 kDa/55 kDa did not correlate either with demographic characteristics, cognitive performances or with motor impairment severity. Truncated Tau production shows a different pattern in PSP compared to other neurodegenerative disorders, supporting the view of disease-specific pathological pathways. These findings are promising in suggesting the identification of a marker for PSP diagnosis in clinical practice.
脑脊液（CSF）中总 Tau 水平在神经退行性疾病中差异很大，因此在鉴别阿尔茨海默病时并无用处。目前尚无用于进行性核上性麻痹（PSP）的脑脊液标志物。本研究的目的是对 Tau 形式进行表征和测量，以验证神经退行性疾病之间的差异模式。该研究纳入了 78 例神经退行性疾病患者和 26 名对照。每位患者均接受了标准化的临床和神经心理学评估、MRI 检查以及脑脊液总 Tau 和磷酸化 Tau 检测。在脑脊液和大脑皮层中，开展了定量免疫沉淀法。识别出了 Tau 的一种延伸形式（55 kDa）和一种截短形式（33 kDa）。对脑脊液样本进行检测，测量两种 Tau 形式的光密度，并计算比值（Tau 比值，33 kDa/55 kDa 形式）。与包括健康受试者（1.16±0.46，P = 0.002）和阿尔茨海默病（1.38±0.68，P < 0.001）在内的对照相比，PSP 患者的 Tau 比值 33 kDa/55 kDa 显著降低，与额颞叶痴呆（0.98±0.30，P = 0.008）或皮质基底节变性综合征（0.98±0.48，P = 0.02）相比也显著降低。此外，在 PSP 患者中，Tau 形式比值低于其他神经退行性锥体外系疾病，如帕金森病（1.16±0.26，P = 0.002）和路易体痴呆（1.44±0.48，P < 0.001）。Tau 比值 33 kDa/55 kDa 与人口统计学特征、认知表现或运动障碍严重程度均无相关性。与其他神经退行性疾病相比，PSP 中截短 Tau 的产生呈现出不同模式，支持了疾病特异性病理途径的观点。这些发现有望提示在临床实践中识别出一种用于 PSP 诊断的标志物。
