Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, D-37075 Göttingen, Germany.
Int J Mol Sci. 2020 Oct 30;21(21):8144. doi: 10.3390/ijms21218144.
Transgenic mouse models represent an essential tool for the exploration of Alzheimer's disease (AD) pathological mechanisms and the development of novel treatments, which at present provide only symptomatic and transient effects. While a variety of mouse models successfully reflects the main neuropathological hallmarks of AD, such as extracellular amyloid-β (Aβ) deposits, intracellular accumulation of Tau protein, the development of micro- and astrogliosis, as well as behavioral deficits, substantial neuron loss, as a key feature of the disease, seems to be more difficult to achieve. In this review, we summarize information on classic and more recent transgenic mouse models for AD, focusing in particular on loss of pyramidal, inter-, and cholinergic neurons. Although the cause of neuron loss in AD is still a matter of scientific debate, it seems to be linked to intraneuronal Aβ accumulation in several transgenic mouse models, especially in pyramidal neurons.
转基因小鼠模型是探索阿尔茨海默病(AD)病理机制和开发新型治疗方法的重要工具,而目前的治疗方法仅提供对症和暂时的效果。虽然各种小鼠模型成功地反映了 AD 的主要神经病理学特征,如细胞外淀粉样蛋白-β(Aβ)沉积、细胞内 Tau 蛋白积累、小胶质细胞和星形胶质细胞的发展以及行为缺陷,但作为该疾病的关键特征的大量神经元丢失似乎更难实现。在这篇综述中,我们总结了关于 AD 的经典和最新的转基因小鼠模型的信息,特别关注锥体神经元、中间神经元和胆碱能神经元的丢失。尽管 AD 中神经元丢失的原因仍在科学争论之中,但似乎与几种转基因小鼠模型中的细胞内 Aβ 积累有关,尤其是在锥体神经元中。