Modeling Alzheimer's Disease: A Review of Gene-Modified and Induced Animal Models, Complex Cell Culture Models, and...

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 Drosophila melanogaster, Caenorhabditis elegans, and Danio rerio. 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.