Timofeeva Anna M, Aulova Kseniya S, Nevinsky Georgy A
SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia.
Brain Sci. 2025 May 5;15(5):486. doi: 10.3390/brainsci15050486.
Alzheimer's disease, a complex neurodegenerative disease, is characterized by the pathological aggregation of insoluble amyloid β and hyperphosphorylated tau. Multiple models of this disease have been employed to investigate the etiology, pathogenesis, and multifactorial aspects of Alzheimer's disease and facilitate therapeutic development. Mammals, especially mice, are the most common models for studying the pathogenesis of this disease in vivo. To date, the scientific literature has documented more than 280 mouse models exhibiting diverse aspects of Alzheimer's disease pathogenesis. Other mammalian species, including rats, pigs, and primates, have also been utilized as models. Selected aspects of Alzheimer's disease have also been modeled in simpler model organisms, such as , , and . It is possible to model Alzheimer's disease not only by creating genetically modified animal lines but also by inducing symptoms of this neurodegenerative disease. This review discusses the main methods of creating induced models, with a particular focus on modeling Alzheimer's disease on cell cultures. Induced pluripotent stem cell (iPSC) technology has facilitated novel investigations into the mechanistic underpinnings of diverse diseases, including Alzheimer's. Progress in culturing brain tissue allows for more personalized studies on how drugs affect the brain. Recent years have witnessed substantial advancements in intricate cellular system development, including spheroids, three-dimensional scaffolds, and microfluidic cultures. Microfluidic technologies have emerged as cutting-edge tools for studying intercellular interactions, the tissue microenvironment, and the role of the blood-brain barrier (BBB). Modern biology is experiencing a significant paradigm shift towards utilizing big data and omics technologies. Computational modeling represents a powerful methodology for researching a wide array of human diseases, including Alzheimer's. Bioinformatic methodologies facilitate the analysis of extensive datasets generated via high-throughput experimentation. It is imperative to underscore the significance of integrating diverse modeling techniques in elucidating pathogenic mechanisms in their entirety.
阿尔茨海默病是一种复杂的神经退行性疾病，其特征是不溶性淀粉样β蛋白的病理性聚集和tau蛋白的过度磷酸化。已采用多种该疾病模型来研究阿尔茨海默病的病因、发病机制和多因素方面，并促进治疗方法的开发。哺乳动物，尤其是小鼠，是在体内研究该疾病发病机制最常用的模型。迄今为止，科学文献已记录了280多种表现出阿尔茨海默病发病机制不同方面的小鼠模型。其他哺乳动物物种，包括大鼠、猪和灵长类动物，也被用作模型。阿尔茨海默病的某些方面也已在更简单的模型生物中建模，如 、 和 。不仅可以通过创建基因改造动物品系来模拟阿尔茨海默病，还可以通过诱导这种神经退行性疾病的症状来建模。本综述讨论了创建诱导模型的主要方法，特别关注在细胞培养物上模拟阿尔茨海默病。诱导多能干细胞（iPSC）技术促进了对包括阿尔茨海默病在内的多种疾病机制基础的新研究。脑组织培养的进展使得能够对药物如何影响大脑进行更个性化的研究。近年来，在复杂细胞系统开发方面取得了重大进展，包括球体、三维支架和微流控培养。微流控技术已成为研究细胞间相互作用、组织微环境和血脑屏障（BBB）作用的前沿工具。现代生物学正经历着向利用大数据和组学技术的重大范式转变。计算建模是研究包括阿尔茨海默病在内的多种人类疾病的有力方法。生物信息学方法有助于分析通过高通量实验生成的大量数据集。必须强调整合多种建模技术以全面阐明致病机制的重要性。
