Exploring efficient and effective mammalian models for Alzheimer's disease.

The aim of this study was to explore and discuss efficient and effective mammalian models for Alzheimer's disease (AD). In this study, efficient AD models are characterized by a small body size, a short lifespan, and rapid development of the main pathology including amyloid plaque formation. Effective AD models are expected to exhibit not only the main pathology, but also co-pathology associated with other neurodegenerative diseases (e.g., Lewy body dementia), systemic disturbances such as disrupted central-peripheral homeostasis, and sleep-circadian failures. This reflects recent findings indicating that AD is far more multifactorial than previously assumed. Although further investigation is required, non-human primates, particularly common marmosets (), and dogs () are candidates of promising and effective AD models. Tree shrews (), guinea pigs (), and evolutionary related species including degus () constitute an alternative group of AD models that remain underexplored but potentially efficient and effective. These mammalian models, together with hypothesis-driven mouse models and advances in data science technologies including omics and imaging analyses, may lead to breakthroughs in AD research, resulting in the development of effective prevention and treatment for AD.