Skoog I, Vanmechelen E, Andreasson L A, Palmertz B, Davidsson P, Hesse C, Blennow K
Department of Clinical Neuroscience, University of Göteborg, Sweden.
Neurodegeneration. 1995 Dec;4(4):433-42. doi: 10.1006/neur.1995.0052.
Alzheimer's disease (AD) is the most common form of dementia, and is characterized by a degeneration of neurones and their synapses, and a higher number of senile plaques (SP) and neurofibrillary tangles (NFT) compared with that found in non-demented individuals of the same age. NFT are composed of a hyperphosphorylated and ubiquitinated form of tau protein. Previous studies have found that in the cerebrospinal fluid (CSF) both tau and ubiquitin are increased in AD. We examined CSF-tau and CSF-ubiquitin in a population based sample of 85-year-olds, 26 demented (11 with probable Alzheimer's disease (AD), 13 with probable vascular dementia (VAD) and 2 with mixed (AD/VAD) type of dementia) and 35 non-demented individuals. CSF-tau was significantly higher both in the probable AD group (254 +/- 113 pg/mL; P < 0.01), and in the probable VAD group (247 +/- 75 pg/mL; P < 0.005), than in the non-demented group (171 +/- 78 pg/mL), but did not significantly differ between the probable AD and probable VAD groups. In contrast, CSF-ubiquitin did not significantly differ between the probable AD (100 +/- 24 ng/mL), probable VAD (102 +/- 16 ng/mL), and non-demented (97 +/- 27 ng/mL) groups. CSF-tau increased with increasing severity of dementia (P < 0.001), though no such relation was found for CSF-ubiquitin. Neither CSF-tau nor CSF-ubiquitin differed between patients with or without the apolipoprotein E E4 isoform. Higher CSF-tau and CSF-ubiquitin levels were also associated with increasing degree of cortical and central brain atrophy as measured by computerized tomography. The relationships between CSF-tau and severity of dementia and to brain atrophy suggest that CSF-tau may be used as a measure of neuronal/axonal degeneration in patients with dementia. We have previously shown a marked increase in both CSF-tau and CSF-ubiquitin in younger patients with AD and VAD. The less pronounced increase in CSF-tau and the lack of difference in CSF-ubiquitin in older patients suggest that the severity of the degenerative process is less in older than in younger demented patients.
阿尔茨海默病（AD）是最常见的痴呆形式，其特征是神经元及其突触退化，与同龄非痴呆个体相比，老年斑（SP）和神经原纤维缠结（NFT）数量更多。NFT由高度磷酸化和泛素化的tau蛋白组成。先前的研究发现，在阿尔茨海默病患者的脑脊液（CSF）中，tau蛋白和泛素均增加。我们在一个基于人群的85岁样本中检测了脑脊液tau蛋白（CSF-tau）和脑脊液泛素（CSF-ubiquitin），其中26人患有痴呆（11人可能患有阿尔茨海默病（AD），13人可能患有血管性痴呆（VAD），2人患有混合型（AD/VAD）痴呆），35人未患痴呆。与未患痴呆组（171±78 pg/mL）相比，可能患有AD组（254±113 pg/mL；P<0.01）和可能患有VAD组（247±75 pg/mL；P<0.005）的CSF-tau显著更高，但可能患有AD组和可能患有VAD组之间无显著差异。相比之下，可能患有AD组（100±24 ng/mL）、可能患有VAD组（102±16 ng/mL）和未患痴呆组（97±27 ng/mL）的CSF-ubiquitin无显著差异。CSF-tau随痴呆严重程度增加而升高（P<0.001），而CSF-ubiquitin未发现这种关系。携带或不携带载脂蛋白E E4亚型的患者，其CSF-tau和CSF-ubiquitin均无差异。通过计算机断层扫描测量，较高的CSF-tau和CSF-ubiquitin水平也与皮质和脑中央萎缩程度增加相关。CSF-tau与痴呆严重程度及脑萎缩之间的关系表明，CSF-tau可作为痴呆患者神经元/轴突退化程度的一个指标。我们先前已表明，患有AD和VAD的年轻患者的CSF-tau和CSF-ubiquitin均显著增加。老年患者CSF-tau升高不太明显且CSF-ubiquitin无差异，这表明老年痴呆患者的退化过程严重程度低于年轻痴呆患者。
