Department of Psychiatry, University of Rostock, Rostock, Germany.
J Alzheimers Dis. 2011;23(2):221-37. doi: 10.3233/JAD-2010-101035.
In vivo imaging of amyloid-β (Aβ) load as a biomarker of Alzheimer's disease (AD) would be of considerable clinical relevance for the early diagnosis and monitoring of treatment effects. Here, we investigated automated quantification of in vivo T2 relaxation time as a surrogate measure of plaque load in the brains of ten AβPP/PS1 transgenic mice (age 20 weeks) using in vivo MRI acquisitions on a 7T Bruker ClinScan magnet. AβPP/PS1 mice present with rapid-onset cerebral β-amyloidosis, and were compared with eight age-matched, wild-type control mice (C57Bl/6J) that do not develop Aβ-deposition in brain. Data were analyzed with a novel automated voxel-based analysis that allowed mapping the entire brain for significant signal changes. In AβPP/PS1 mice, we found a significant decrease in T2 relaxation times in the deeper neocortical layers, caudate-putamen, thalamus, hippocampus, and cerebellum compared to wildtype controls. These changes were in line with the histological distribution of cerebral Aβ plaques and activated microglia. Grey matter density did not differ between wild-type mice and AβPP/PS1 mice, consistent with a lack of neuronal loss in histological investigations. High-field MRI with automated mapping of T2 time changes may be a useful tool for the detection of plaque load in living transgenic animals, which may become relevant for the evaluation of amyloid lowering intervention effects in future studies.
体内成像淀粉样蛋白-β（Aβ）负荷作为阿尔茨海默病（AD）的生物标志物，对于早期诊断和治疗效果监测具有重要的临床意义。在这里，我们使用 Bruker ClinScan 磁体上的 7T 活体 MRI 采集，研究了自动量化活体 T2 弛豫时间作为斑块负荷的替代指标在 10 只 AβPP/PS1 转基因小鼠（20 周龄）脑中的应用。AβPP/PS1 小鼠表现出快速发作的脑β淀粉样蛋白病，并与 8 只年龄匹配的野生型对照小鼠（C57Bl/6J）进行比较，后者在脑中不会发生 Aβ沉积。使用一种新的自动体素分析方法对数据进行了分析，该方法允许对整个大脑进行显著信号变化的映射。在 AβPP/PS1 小鼠中，与野生型对照组相比，我们发现深层皮质层、尾状核、丘脑、海马体和小脑的 T2 弛豫时间明显降低。这些变化与大脑 Aβ斑块和激活的小胶质细胞的组织分布一致。与组织学研究中神经元缺失一致，野生型小鼠和 AβPP/PS1 小鼠之间的灰质密度没有差异。高场 MRI 结合 T2 时间变化的自动映射可能是检测活体转基因动物斑块负荷的有用工具，这可能在未来的研究中对评估淀粉样蛋白降低干预效果具有重要意义。
