Abstract:
Concerns about poor animal to human translation have come increasingly to the fore, in particular with regards to cognitive improvements in rodent models, which have failed to translate to meaningful clinical benefit in humans. This problem has been widely acknowledged, most recently in the field of Alzheimer\'s disease, although this issue pervades the spectrum of central nervous system (CNS) disorders, including neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. Consequently, recent efforts have focused on improving preclinical to clinical translation by incorporating more clinically analogous outcome measures of cognition, such as touchscreen-based assays, which can be employed across species, and have great potential to minimize the translational gap. For aging-related research, it also is important to incorporate model systems that facilitate the study of the long prodromal phase in which cognitive decline begins to emerge and which is a major limitation of short-lived species, such as laboratory rodents. We posit that to improve translation of cognitive function and dysfunction, nonhuman primate models, which have conserved anatomical and functional organization of the primate brain, are necessary to move the field of translational research forward and to bridge the translational gaps. The present studies describe the establishment of a comprehensive battery of touchscreen-based tasks that capture a spectrum of domains sensitive to detecting aging-related cognitive decline, which will provide the greatest benefit through longitudinal evaluation throughout the prolonged lifespan of the marmoset.
摘要:
人们越来越关注动物对人类的翻译,特别是关于啮齿动物模型的认知改善,未能转化为对人类有意义的临床益处。这个问题已经被广泛承认,最近在阿尔茨海默病领域,尽管这个问题遍及中枢神经系统(CNS)疾病的范围,包括神经发育,神经精神病学,和神经退行性疾病。因此,最近的努力集中在通过纳入更多临床类似的认知结果测量来改善临床前到临床的翻译,例如基于触摸屏的检测,可以跨物种使用,并且有很大的潜力来最小化平移间隙。对于与衰老相关的研究,纳入模型系统也很重要,这些模型系统有助于研究认知衰退开始出现的长期前驱阶段,这是短命物种的主要限制,如实验室啮齿动物。我们认为,为了改善认知功能和功能障碍的翻译,非人灵长类动物模型,它们具有灵长类动物大脑的保守解剖和功能组织,是推动平移研究领域向前发展和弥合平移差距的必要条件。本研究描述了建立一套全面的基于触摸屏的任务,这些任务捕获了一系列对检测与衰老相关的认知衰退敏感的领域,这将提供最大的好处,通过纵向评估,在整个使用寿命延长的the猴。