Baltes Christof, Princz-Kranz Felicitas, Rudin Markus, Mueggler Thomas
Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland.
Methods Mol Biol. 2011;711:511-33. doi: 10.1007/978-1-61737-992-5_26.
One of the major neuropathological changes characteristic of Alzheimer's disease (AD) is deposits of beta-amyloid plaques and neurofibrillary tangles in neocortical and subcortical regions of the AD brain. The histochemical detection of these lesions in postmortem brain tissue is necessary for definitive diagnosis of AD. Methods for their in vivo detection would greatly aid the diagnosis of AD in early stages when neuronal loss and related functional impairment are still limited and would also open the opportunity for effective therapeutic interventions. Magnetic resonance imaging (MRI) theoretically provides the spatial resolution needed to resolve amyloid-β plaques. Although currently limited for clinical applications due to unfavorable long acquisition times, MRI has been used to visualize Aβ plaques in AD mouse models. The ability to detect amyloid-positive brain lesions in vivo using non-invasive imaging would allow to track disease progression and to monitor the efficacy of potential therapies in disease-modifying studies using transgenic models resembling AD pathology. Here, we provide MRI protocols for in vivo (mouse) and ex vivo (AD tissue samples) amyloid plaque imaging and the procedure for correlating these with thioflavin-S and iron-staining histology. Current challenges and limitations are discussed.
阿尔茨海默病（AD）的主要神经病理学变化之一是在AD大脑的新皮质和皮质下区域出现β-淀粉样蛋白斑块和神经原纤维缠结。在死后脑组织中对这些病变进行组织化学检测对于AD的明确诊断是必要的。在体内检测这些病变的方法将极大地有助于在神经元丢失和相关功能损害仍然有限的早期阶段诊断AD，并且还将为有效的治疗干预提供机会。磁共振成像（MRI）理论上提供了分辨淀粉样β蛋白斑块所需的空间分辨率。尽管目前由于采集时间长而不利于临床应用，但MRI已被用于在AD小鼠模型中可视化Aβ斑块。使用非侵入性成像在体内检测淀粉样蛋白阳性脑病变的能力将有助于追踪疾病进展，并在使用类似于AD病理学的转基因模型进行疾病修饰研究中监测潜在疗法的疗效。在这里，我们提供了用于体内（小鼠）和体外（AD组织样本）淀粉样蛋白斑块成像的MRI方案，以及将这些与硫黄素-S和铁染色组织学相关联的程序。讨论了当前的挑战和局限性。
