ZHANG Jian-Dong, GU Ze-Long, YAO Yi-Ran, LI Wei
神经药理学报. 2025, 15(03): 53-54.
Alzheimer's disease(AD) is a prevalent neurodegenerative disease that poses a serious threat to the health of the elderly. The pathogenesis of AD is complex and not yet fully prevalent. Establishing appropriate animal models is of great significance for the indepth investigation of its pathogenesis and the search for effective therapeutic strategies. In recent years, various animal models of AD have been commonly used, including natural models, genetically engineered models, and chemically induced models. Each of them has its advantages and disadvantages in simulating the pathological features and cognitive dysfunction of AD. And this requires the application of different animals, such as mice, rats, and non-human primates for AD research. Mouse models are extensively utilized owing to their significant advantages. Their genomes show a high degree of similarity to those of humans, enabling them to effectively replicate the genetic basis of the disease. Mice are small in size, have rapid reproductive cycles, and possess short lifespans, making them ideal for large-scale and long-term studies. Moreover, their genetic manipulation techniques are well-established, providing a diverse array of model options that serve as a robust foundation for disease simulation and mechanistic research. Additionally, cognitive behavior analysis in mice is straightforward and can be closely correlated with pathological changes in the brain, thereby facilitating the evaluation of disease progression and therapeutic efficacy. Mouse models such as Tg2576, 5xFAD and 3xTg-AD, by simulating the pathological features and cognitive dysfunction of human AD, provide an important foundation for studying the pathogenesis of AD, drug screening and the development of treatment methods. Compared with mice, rats exhibit greater physiological and genetic similarity to humans. Their larger body and brain volume make experimental operations more convenient, including intrathecal administration, microdialysis, multiple samplings, and in vivo electrophysiological studies. Furthermore, rats' motor coordination and behavioral patterns are closer to those of humans, allowing for a more comprehensive assessment of the impact of AD on behavior. The TgF344-AD rat model, a double transgenic model carrying two human gene mutations, displays neuropathological changes similar to those observed in human AD. In addition, the Mac mulacaatta, as a non-human primate model, holds unique advantages in AD research. With a longer lifespan, it permits long-term longitudinal studies to observe the development process of AD. By injecting adeno-associated viruses carrying specific tau mutations into the brains of Macaca mulatta, tau pathological changes similar to those in AD can be induced, encompassing the misfolding, phosphorylation, aggregation of tau proteins, and the formation of neurofibrillary tangles. Zebrafish, highly similar to humans in terms biology of, structure, function, and genetics, has emerged as an extremely attractive model for studying human diseases. It is small in size, has a high reproductive capacity, is easy to breed, and its embryos and larvae are transparent, making it suitable for high-throughput drug screening. In conclusion, different animal models each possess their own distinct characteristics and advantages. Future research should integrate the strengths of multiple models to more comprehensively simulate the complex pathological process of human AD and thereby promote the development of effective treatment methods.
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