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Disease Mechanisms: Cognitive resilience (Milestone 2.K)


Timeline Start - End

2016 - 2020

Research Implementation Area

Research on Disease Mechanisms

Create new research programs that use data-driven, network biology approaches aimed at understanding the (epi)genetics and complex biology of cognitive resilience in individuals with high genetic risk for dementia and in individuals with exceptional longevity.

Success Criteria

  • Launch at least 6 research projects aimed at identifying molecular networks causally linked to cognitive resilience as potential therapeutic targets for disease prevention. These efforts should support the preclinical validation of the identified targets.

Summary of Key Accomplishments

The development of effective treatment and prevention for complex diseases such as AD can benefit from a deeper understanding of which genetic, environmental, social, and behavioral factors promote wellness and resilience against disease. Established through a targeted research initiative, the Resilience-AD Program supports 10 cross-disciplinary projects using a big data approach to understand why some individuals who are at high risk of AD due to genetic factors (two copies of ApoE4), very old age (90+, centenarians) or the presence of AD biomarkers (accumulation of amyloid and tau in the brain) remain dementia-free compared to their peers. Research supported through this program has identified several new biological pathways that may protect the brain from the effects of amyloid accumulation, such as genes involved in bile acid metabolism.

The key accomplishments summary is current as of March 2022. 

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