Animal Models of Alzheimer's Disease: Current Strategies and New Directions

Animal models constructed based on pathogenic factors have promoted drug development for Alzheimer’s disease (AD). The transgenic models in use, mainly mice, reproduce pathological phenotypes by introducing gene mutations identified in familial cases. These models have facilitated the assessment of drug efficacy and provided a platform for mechanistic studies. However, the issue of species differences, coupled with the strong heterogeneity of AD etiology, poses a challenge for these animal models, ultimately affecting drug development. Here, we present a comprehensive overview of widely utilized rodent (Mouse and Rat) and non-rodent models (Danio rerio (Zebrafish), Drosophila melanogaster (Drosophila), and C. elegans), highlighting their phenotype characteristics and corresponding applications. By examining the limitations inherent in these models, we also introduce various existing strategies for modeling AD in diverse species, highlighting the advances of non-human primates (NHP). Furthermore, we emphasize the potential insights from the integration of innovative technologies in AD research, while also providing valuable perspectives on the future development of AD animal models.