Buerger Katharina, Ewers Michael, Pirttilä Tuula, Zinkowski Raymond, Alafuzoff Irina, Teipel Stefan J, DeBernardis John, Kerkman Daniel, McCulloch Cheryl, Soininen Hilkka, Hampel Harald
Dementia Research Section and Memory Clinic, Alzheimer Memorial Center, Department of Psychiatry, Ludwig-Maximilian University Munich, Germany.
Brain. 2006 Nov;129(Pt 11):3035-41. doi: 10.1093/brain/awl269. Epub 2006 Sep 29.
Hyperphosphorylated tau protein (P-tau) in CSF is a core biomarker candidate of Alzheimer's disease. Hyperphosphorylation of tau is thought to lead to neurofibrillary changes, a neuropathological hallmark of this type of dementia. Currently, the question is unresolved whether CSF levels of P-tau reflect neurofibrillary changes within the brain of a patient with the illness. Twenty-six patients were included with intra-vitam CSF as well as post-mortem neuropathological data. In the CSF, P-tau phosphorylated at threonine 231 (P-tau231P) was analysed. Post-mortem, scores of neurofibrillary tangles (NFT) and neuritic plaques (NP) were assessed in frontal, temporal, parietal and hippocampal cortical areas. In the same cortical regions, load of hyperphosphorylated tau protein (HP-tau load) was determined. Concentrations of P-tau231P were measured in frontal cortex homogenates. We found significant correlations between CSF P-tau231P concentrations and scores of NFTs and HP-tau load in all neocortical regions studied. The score of NPs was correlated with CSF P-tau231P only within the frontal cortex. There was a correlation between P-tau231P in CSF and brain homogenates. These findings indicate that CSF P-tau231P may serve as an in vivo surrogate biomarker of neurofibrillary pathology in Alzheimer's disease.
脑脊液中的高磷酸化tau蛋白（P-tau）是阿尔茨海默病核心生物标志物候选物。tau蛋白的过度磷酸化被认为会导致神经原纤维变化，这是这类痴呆症的神经病理学特征。目前，脑脊液中P-tau水平是否反映患病患者大脑内的神经原纤维变化这一问题尚未解决。纳入了26例患者，他们有生前脑脊液以及死后神经病理学数据。在脑脊液中，分析了苏氨酸231位点磷酸化的P-tau（P-tau231P）。死后，在额叶、颞叶、顶叶和海马皮质区域评估神经原纤维缠结（NFT）和神经炎性斑块（NP）的评分。在相同皮质区域，测定高磷酸化tau蛋白负荷（HP-tau负荷）。在额叶皮质匀浆中测量P-tau231P的浓度。我们发现在所有研究的新皮质区域，脑脊液P-tau231P浓度与NFT评分和HP-tau负荷之间存在显著相关性。NP评分仅在额叶皮质内与脑脊液P-tau231P相关。脑脊液中的P-tau231P与脑匀浆之间存在相关性。这些发现表明，脑脊液P-tau231P可能作为阿尔茨海默病神经原纤维病理的体内替代生物标志物。
