Data Sheet 1_Exploring efficient and effective mammalian models for Alzheimer’s disease.pdf

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 (Callithrix jacchus), and dogs (Canis lupus familiaris) are candidates of promising and effective AD models. Tree shrews (Tupaia belangeri), guinea pigs (Cavia porcellus), and evolutionary related species including degus (Octodon 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.

本研究旨在探索并探讨适用于阿尔茨海默病（Alzheimer’s Disease，AD）的高效且有效的哺乳动物模型。本研究中，高效AD模型的特征为体型小巧、寿命较短，且包括淀粉样斑块形成在内的核心病理进程进展迅速。有效的AD模型不仅需展现上述核心病理特征，还应呈现与其他神经退行性疾病（如路易体痴呆）相关的共病理特征，以及中枢-外周稳态破坏等系统紊乱与睡眠-昼夜节律失调。这契合近期研究发现，即AD的致病因素远较此前假设更为多元复杂。尽管仍需开展进一步研究，但非人灵长类动物——尤其是普通狨猴（Callithrix jacchus）与家犬（Canis lupus familiaris）——已成为极具前景的有效AD模型候选者。树鼩（Tupaia belangeri）、豚鼠（Cavia porcellus）以及包括八齿鼠（Octodon degus）在内的近缘物种，则构成了另一组尚未得到充分探索，但兼具高效性与有效性的AD模型候选群体。上述哺乳动物模型，结合假说驱动型小鼠模型以及组学、成像分析等数据科学技术的进展，有望推动AD研究领域取得突破性进展，进而开发出针对AD的有效预防与治疗方案。