T1? MRI AS A MARKER FOR NEUROFIBRILLARY TANGLES IN A MOUSE MODEL OF AD

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 AD小鼠模型模仿淀粉样β蛋白或过度磷酸化的tau病理， 阿尔茨海默病(AD)的尸检诊断标记物 使用生化和组织学技术。然而，唯一报道的MRI特征 在转基因AD小鼠模型上已经研究了淀粉样β蛋白的病理机制。松弛测量法 阿尔茨海默病患者T1？松弛时间的研究表明，T1？松弛时间相差8% 内侧颞叶白质松弛时间为5%，灰质松弛时间为5%。它是 假设T1？松弛时间常数对病理变化也很敏感 Tau蛋白导致细胞内病变引起的生化变化 神经原纤维缠结(NFTs)。为了验证这一假设，我们目前正在研究一组 在人tau亚型中表达P301S突变的转基因(TG)tau小鼠，以及 年龄匹配的野生型(WT)小鼠，进行T1？MRI检查。 所有的动物研究都得到了IACUC的批准。转基因动物是从PS19品系中选育出来的 P301S型号。瓦里安在9.4T小口径扫描仪上对老龄小鼠进行了MRI检查 13-15个月。在自旋锁定时间ts1=1，20， 30、40ms用于量化T1？松弛时间常数。四种MRI对比度分别是 在逐个像素的基础上进行指数拟合，以创建T1的颜色编码参数图 在每个像素上。在T1加权图像上手动绘制海马区和大脑皮层的ROI图 将TSL=1ms的图像和蒙版应用于T1？映射到的相应切片 测量平均T1？松弛时间。对PS19进行免疫组织化学染色 取小鼠脑后，以验证tau的病理程度。磷酸化tau的抗体被染成棕色，苏木素反染用于可视化。 神经元核团。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. AD mouse models mimicking, either the amyloid-beta or hyperphosphorylated tau pathologies, the post-mortem diagnostic markers of Alzheimer's disease (AD), have been characterized using biochemical and histological techniques. However, the only MRI characterization reported on transgenic mouse models of AD have studied the amyloid-beta pathology. A relaxometry study of the T1¿ relaxation time in human AD patients showed a difference of 8% in the T1¿ relaxation times of white matter and 5% in gray matter of the medial temporal lobe. It is hypothesized that the T1¿ relaxation time constant is also sensitive to the pathologic biochemical changes resulting from pathology due to tau protein that leads to intracellular neurofibrillary tangles (NFTs). To test this hypothesis, we are currently studying a cohort of transgenic (Tg) tau mice expressing the P301S mutation in a human tau isoform, and age-matched wild-type (WT) mice with T1¿ MRI. All animal studies were approved by the IACUC. Tg animals were bred from the PS19 line of the P301S model. MRI was performed on a 9.4T small-bore scanner by Varian on mice aged 13-15 months. Four T1¿-weighted images were obtained, at spin-locking times of TSL=1, 20, 30, 40ms for quantifying T1¿ relaxation time constant. The four MRI contrasts were exponentially fit on a pixel-by-pixel basis to create a color-coded parametric map of the T1¿ at each pixel. ROIs of the hippocampus and cortex were manually drawn on T1¿-weighted images at TSL=1ms, and masks were applied to the corresponding slices in the T1¿ maps to measure the mean T1¿ relaxation times. Immunohistochemistry was performed on the PS19 mice after harvesting the brain in order to verify the extent of tau pathology. An antibody for phosphorylated tau stained brown and a counter-stain with hematoxylin were used to visualize neuronal nuclei.