Translational approaches to understanding resilience to Alzheimer's disease. Issue 5 (May 2022)

• Record Type: Journal Article
• Authors: Neuner, Sarah M.; Telpoukhovskaia, Maria; Menon, Vilas; O'Connell, Kristen M.S.; Hohman, Timothy J.; Kaczorowski, Catherine C.
• Is Part Of: Trends in neurosciences. Volume 45:Issue 5(2022)
• Page Start: 369
• Page End: 383
• Publication Date: 2022-05
• Subjects: genetic diversity -- mouse models -- cognition -- pathology -- tau -- amyloid; Neurology -- Periodicals; Neurophysiology -- Periodicals; Neurobiology -- Periodicals; 612.8
• DOI: 10.1016/j.tins.2022.02.005
• Languages: English
• ISSNs: 0166-2236

Abstract

Abstract : 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. Highlights: Some individuals retain cognitive function despite high levels of Alzheimer's disease (AD) pathology. Understanding the biology behind this form of 'AD resilience' may lead to opportunities for therapeutic development. Human genetic studies and postmortem analyses have identified a number of factors associated with cognitive resilience to AD pathology, including overall maintenance of synapse structure and candidate molecular mediators (e.g., REST, NRN1, among others). Genetically and phenotypically diverse mouse models of AD provide new and translationally relevant opportunities to identify and prioritize new resilience mechanisms. Approaches integrating results from both human and mouse studies will provide an effective path toward the development of therapeutics promoting resilience in susceptible human populations.