疑似正常压力脑积水老年患者中磷酸化 Tau 蛋白的小脑延髓池-腰椎梯度较小。
Small cisterno-lumbar gradient of phosphorylated Tau protein in geriatric patients with suspected normal pressure hydrocephalus.
作者信息
Djukic Marija, Spreer Annette, Lange Peter, Bunkowski Stephanie, Wiltfang Jens, Nau Roland
机构信息
Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, Göttingen, Germany.
Institute of Neuropathology, University Medical Center Goettingen (UMG), Robert-Koch-Strasse 40, D-37075, Göttingen, Germany.
出版信息
Fluids Barriers CNS. 2016 Aug 31;13(1):15. doi: 10.1186/s12987-016-0039-9.
BACKGROUND
The composition of the cerebrospinal fluid (CSF) is not homogeneous, and concentrations of proteins from different origins diverge among ventricular, cisternal and lumbar CSF fractions. Concentrations of blood-derived proteins increase and of brain-derived proteins decrease from ventricular to lumbar fractions. We studied whether the origin of the CSF portion analysed may affect results in CSF analysis for dementia.
METHODS
In 16 geriatric patients with suspected normal pressure hydrocephalus [age 82.5 (76/87) years; median (25th/75th percentile)] a lumbar spinal tap of 40 ml was performed. The CSF was sequentially collected in 8 fractions of 5 ml with the 1st fraction corresponding to lumbar CSF, the 8th to cisterna magna-near CSF. Fractions were analysed for total protein, albumin, Tau protein (Tau), phosphorylated Tau (pTau), Amyloid beta 1-42 (Aβ1-42), Amyloid beta 1-40 (Aβ1-40), and the Aβ1-42/Aβ1-40 ratio.
RESULTS
The concentrations of total protein and albumin increased from cisternal to lumbar fractions due to diffusion-related accumulation from blood to CSF with significantly higher concentrations in fraction 1 compared to fraction 8. The concentrations of Tau showed a non-significant trend towards decreased values in lumbar samples, and pTau was slightly, but significantly decreased in the lumbar fraction 1 [26.5 (22.5/35.0) pg/ml] compared to the cistern-near fraction 8 [27.0 (24.2/36.3) pg/ml] (p = 0.02, Wilcoxon signed rank test). Aβ1-42, Aβ1-40, and the Aβ1-42/Aβ1-40 ratio remained almost constant.
CONCLUSIONS
According to the flow-related diverging dynamics of blood-derived and brain-derived proteins in CSF, the concentrations of Tau and pTau tended to be lower in lumbar compared to cisternal CSF fractions after a spinal tap of 40 ml. The differences reached statistical significance for pTau only. The small differences will not affect clinical interpretation of markers of dementia in the vast majority of cases.
背景
脑脊液（CSF）的成分并非均匀一致，不同来源蛋白质的浓度在脑室、脑池和腰段脑脊液组分中存在差异。从脑室到腰段组分，血液来源蛋白质的浓度升高，而脑来源蛋白质的浓度降低。我们研究了所分析的脑脊液部分的来源是否会影响痴呆脑脊液分析的结果。
方法
对16例疑似正常压力脑积水的老年患者[年龄82.5（76/87）岁；中位数（第25/75百分位数）]进行了40毫升的腰椎穿刺。脑脊液按顺序收集成8个5毫升的组分，第1个组分对应腰段脑脊液，第8个组分对应枕大池附近的脑脊液。对各组分进行总蛋白、白蛋白、Tau蛋白（Tau）、磷酸化Tau蛋白（pTau）、淀粉样β蛋白1-42（Aβ1-42）、淀粉样β蛋白1-40（Aβ1-40）以及Aβ1-42/Aβ1-40比值的分析。
结果
由于血液到脑脊液的扩散相关积聚，总蛋白和白蛋白的浓度从脑池组分到腰段组分升高，第1组分中的浓度显著高于第8组分。Tau蛋白的浓度在腰段样本中呈非显著下降趋势，与枕大池附近的第8组分[27.0（24.2/36.3）皮克/毫升]相比，腰段第1组分中的pTau蛋白略有下降，但差异显著[26.5（22.5/35.0）皮克/毫升]（p = 0.02，Wilcoxon符号秩检验）。Aβ1-42、Aβ1-40以及Aβ1-42/Aβ1-40比值几乎保持不变。
结论
根据脑脊液中血液来源和脑来源蛋白质与流动相关的不同动态变化，在抽取40毫升脑脊液后，腰段脑脊液中Tau蛋白和pTau蛋白的浓度相较于脑池脑脊液组分往往更低。仅pTau蛋白的差异具有统计学意义。在绝大多数情况下，这些微小差异不会影响痴呆标志物的临床解读。
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