Radde Rebecca, Duma Cecilia, Goedert Michel, Jucker Mathias
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Otfried-Müller Strasse 27, Tübingen, Germany.
Eur J Nucl Med Mol Imaging. 2008 Mar;35 Suppl 1:S70-4. doi: 10.1007/s00259-007-0704-y.
To study Alzheimer's disease (AD), a variety of mouse models has been generated through the overexpression of the amyloid precursor protein and/or the presenilins harboring one or several mutations found in familial AD. With aging, these mice develop several lesions similar to those of AD, including diffuse and neuritic amyloid deposits, cerebral amyloid angiopathy, dystrophic neurites and synapses, and amyloid-associated neuroinflammation. Other characteristics of AD, such as neurofibrillary tangles and nerve cell loss, are not satisfactorily reproduced in these models. Mouse models that recapitulate only specific aspects of AD pathogenesis are of great advantage when deciphering the complexity of the disease and can contribute substantially to diagnostic and therapeutic innovations. Incomplete mouse models have been key to the development of Abeta42-targeted therapies, as well as to the current understanding of the interrelationship between cerebral beta-amyloidosis and tau neurofibrillary lesions, and are currently being used to develop novel diagnostic agents for in vivo imaging.
为了研究阿尔茨海默病（AD），通过过表达淀粉样前体蛋白和/或早老素生成了多种小鼠模型，这些早老素携带在家族性AD中发现的一个或几个突变。随着年龄增长，这些小鼠会出现几种与AD相似的病变，包括弥漫性和神经炎淀粉样沉积、脑淀粉样血管病、营养不良性神经突和突触，以及淀粉样蛋白相关的神经炎症。AD的其他特征，如神经原纤维缠结和神经细胞丢失，在这些模型中并未得到令人满意的重现。当解读该疾病的复杂性时，仅概括AD发病机制特定方面的小鼠模型具有很大优势，并且可以为诊断和治疗创新做出重大贡献。不完全的小鼠模型一直是针对β淀粉样蛋白42（Aβ42）疗法发展的关键，也是目前对脑β淀粉样变性与tau神经原纤维病变之间相互关系理解的关键，并且目前正被用于开发用于体内成像的新型诊断剂。
