Translational approaches to understanding resilience to Alzheimer’s disease

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.