CSF phospho-tau correlates with behavioural decline and brain insoluble phospho-tau levels in a rat model of tauopathy.
CSF phospho-tau correlates with behavioural decline and brain insoluble phospho-tau levels in a rat model of tauopathy.
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在 tau 病大鼠模型中，CSF 磷酸 tau 与行为下降和脑不溶性磷酸 tau 水平相关。
DOI：
10.1007/s00401-010-0680-3
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发表时间：
2010
影响因子：
12.7
通讯作者：
Novak,Michal
中科院分区：
文献类型：
--
作者：
Zilka,Norbert;Korenova,Miroslava;Kovacech,Branislav;Iqbal,Khalid;Novak,Michal
本研究的目的是在表达人截断tau蛋白的转基因大鼠中，确定进行性神经行为衰退与脑脊液（CSF）和大脑中磷酸化tau蛋白水平（p-tau181）之间的关系。行为分析采用NeuroScale评分方法进行量化，结果显示转基因大鼠根据基线行为功能分为两组：(1)轻度神经行为障碍（MNI，评分3.3-26）和(2)重度神经行为障碍（SNI，评分36-44）。SNI转基因大鼠的脑萨科基不溶性p-tau181含量明显高于MNI转基因大鼠。为了确定脑脊液磷酸化tau是否反映了大脑中萨科齐不溶性tau的行为下降和增加，在一项纵向研究中测量了脑脊液中的p-tau181。该研究显示，在从MNI到SNI的疾病进展过程中，CSF p-tau181显著增加。此外，脑脊液中p-tau181水平的增加与大脑中萨科齐不溶性p-tau181水平的增加相关。在进行性行为下降过程中，脑脊液p-tau181水平的升高表明，它可能是临床前药物开发的有用替代生物标志物，也是阿尔茨海默病和相关人类tau病的疾病改善治疗临床试验的潜在替代终点。
The aim of the present study was to identify the relationship between progressive neurobehavioural decline and phospho-tau levels (p-tau181) in the cerebrospinal fluid (CSF) and the brain in transgenic rats expressing human truncated tau protein. Behavioural analyses, as quantified using the NeuroScale scoring method, revealed that the transgenic rats fell into two main groups based on the baseline behavioural functioning: (1) mild neurobehavioural impairment (MNI, score 3.3–26) and (2) severe neurobehavioural impairment (SNI, score 36–44). SNI transgenic rats showed a significant increase in brain sarkosyl insoluble p-tau181when compared to their MNI counterparts. In order to determine whether CSF phospho-tau reflects the behavioural decline and increase in sarkosyl insoluble tau in the brain, p-tau181was measured in the CSF in a longitudinal study. The study showed a significant increase in CSF p-tau181during the progression of the disease from MNI to SNI. Moreover, increased levels of p-tau181in CSF correlated with an increase in the sarkosyl insoluble p-tau181levels in the brain. The increase in the CSF level of p-tau181during progressive behavioural decline suggests that it may represent a useful surrogate biomarker for preclinical drug development and a potential surrogate endpoint for clinical trials of disease-modifying therapy for Alzheimer’s disease and related human tauopathies.