Objective

Brain calcifications are associated with several neurodegenerative diseases. Here, we describe the occurrence of intracranial calcifications as a new phenotype in transgenic P301L mice overexpressing four repeat tau, a model of human tauopathy.

Materials and methods

Thirty-six P301L mice (Thy1.2) and ten age-matched non-transgenic littermates of different ages were assessed. Gradient echo data were acquired in vivo and ex vivo at 7 T and 9.4 T for susceptibility-weighted imaging (SWI) and phase imaging. In addition, ex vivo micro-computed tomography (μCT) was performed. Histochemistry and immunohistochemistry were used to investigate the nature of the imaging lesions.

Results

SW images revealed regional hypointensities in the hippocampus, cortex, caudate nucleus, and thalamus of P301L mice, which in corresponding phase images indicated diamagnetic lesions. Concomitantly, µCT detected hyperdense lesions, though fewer lesions were observed compared to MRI. Diamagnetic susceptibility lesions in the hippocampus increased with age. The immunochemical staining of brain sections revealed osteocalcin-positive deposits. Furthermore, intra-neuronal and vessel-associated osteocalcin-containing nodules co-localized with phosphorylated-tau (AT8 and AT100) in the hippocampus, while vascular osteocalcin-containing nodules were detected in the thalamus in the absence of phosphorylated-tau deposition.

Discussion

SWI and phase imaging sensitively detected intracranial calcifications in the P301L mouse model of human tauopathy.

中文翻译：

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SWI 和相位成像揭示了人类 tau 蛋白病 P301L 小鼠模型中的颅内钙化。

客观的

脑钙化与多种神经退行性疾病有关。在这里，我们将颅内钙化的发生描述为过表达四个重复 tau 的转基因 P301L 小鼠中的一种新表型，这是一种人类 tau 蛋白病模型。

材料和方法

评估了 36 只 P301L 小鼠 (Thy1.2) 和 10 只年龄匹配的不同年龄的非转基因同窝仔鼠。梯度回波数据是在体内和体外在 7 T 和 9.4 T 下采集的，用于磁化率加权成像 (SWI) 和相位成像。此外，还进行了离体微计算机断层扫描 (μCT)。组织化学和免疫组织化学用于研究成像病变的性质。

结果

SW 图像显示 P301L 小鼠海马、皮质、尾状核和丘脑的区域性低信号，在相应的相位图像中显示抗磁性病变。同时，μCT 检测到高密度病变，但与 MRI 相比观察到的病变较少。海马中的抗磁易感性病变随着年龄的增长而增加。脑切片的免疫化学染色显示骨钙素阳性沉积物。此外，神经元内和血管相关的含有骨钙素的结节与海马中的磷酸化 tau（AT8 和 AT100）共定位，而在没有磷酸化 tau 沉积的情况下，在丘脑中检测到含有血管骨钙素的结节。

讨论

SWI 和相位成像灵敏地检测到 P301L 人类 tau 蛋白病小鼠模型中的颅内钙化。