Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Trends Neurosci. 2022 May;45(5):369-383. doi: 10.1016/j.tins.2022.02.005. Epub 2022 Mar 17.
Individuals who maintain cognitive function despite high levels of Alzheimer's disease (AD)-associated pathology are said to be 'resilient' to AD. Identifying mechanisms underlying resilience represents an exciting therapeutic opportunity. Human studies have identified a number of molecular and genetic factors associated with resilience, but the complexity of these cohorts prohibits a complete understanding of which factors are causal or simply correlated with resilience. Genetically and phenotypically diverse mouse models of AD provide new and translationally relevant opportunities to identify and prioritize new resilience mechanisms for further cross-species investigation. This review will discuss insights into resilience gained from both human and animal studies and highlight future approaches that may help translate these insights into therapeutics designed to prevent or delay AD-related dementia.
尽管存在高水平的阿尔茨海默病（AD）相关病理，但仍能保持认知功能的个体被称为对 AD 具有“弹性”。确定弹性背后的机制代表了一个令人兴奋的治疗机会。人类研究已经确定了许多与弹性相关的分子和遗传因素，但这些队列的复杂性使得无法完全了解哪些因素是因果关系，还是仅仅与弹性相关。具有遗传和表型多样性的 AD 小鼠模型为进一步跨物种研究提供了新的、具有转化相关性的机会，以确定和优先考虑新的弹性机制。这篇综述将讨论从人类和动物研究中获得的关于弹性的见解，并强调未来可能有助于将这些见解转化为旨在预防或延缓 AD 相关痴呆症的治疗方法的方法。
