Understanding Brain Resiliency to Improve the Experience of Aging

By Olivia Ramirez

The brain has vast and innumerable complexities in its structure and function. Dr. Michael McConnell is one of the scientists working to better understand the brain and more specifically why some brains retain full function despite showing signs of Alzheimer’s disease post-mortem.

McConnell has always been interested in brain development. In graduate school, he studied the topic in the context of psychiatric diseases. New findings from his own lab led him to focus on the aging phenotype: the neurons he studies are selectively vulnerable to age-related atrophy.  

After Dr. Daniel Weinberger, a National Academy of Medicine (NAM) member and project teammate, recruited Dr. McConnell to the Lieber Institute, he shared the announcement of the Healthy Longevity Global Competition. They both saw the Catalyst Competition as a way to expand the project on resilient brains and an opportunity to make an impact in the field of healthy longevity.

Michael McConnell (center) and his team

Resilient Brains: New Insights for Healthy Brain Aging, McConnell’s NAM Healthy Longevity Catalyst Award winning project aims to identify mechanisms that contribute to resilience in some individuals and determine how they can drive that same resilience in everyone. Of the 3,000 brains examined through the Lieber Institute’s brain repository, about 25 showed the hallmarks of Alzheimer’s disease in patients who didn’t exhibit the cognitive decline and other symptoms associated with the illness. Further studies revealed that about half of those 25 patients had living fibroblast cell lines, a connective tissue, that could be cultured and reprogrammed to pluripotency. The ultimate goal of this project, and the next phase of the work, is to study neurons derived from the fibroblast cultures on a molecular level to better understand the genetic underpinnings of resilience to Alzheimer’s disease and, ultimately, find new targets for intervention.

As McConnell sees it, a lot of progress has been made with regard to once terminal diseases, like cancer and HIV/AIDS. These have now (in many cases) become chronic diseases that can be effectively treated and managed. However, similar progress hasn’t been made with respect to brain health. Cognitive decline is common, and nearly inevitable as people live longer, but the understanding of neurological diseases has been slow to develop. McConnell hopes his project will help to change that trajectory.

Throughout his career, McConnell has contributed to our understanding of human diseases. With the funding he’s received from the NAM Catalyst Award, he plans to dedicate more time to learning from patients with asymptomatic Alzheimer’s disease and extend this to other aging-related brain disorders. His work ultimately has the potential to help the 47 million people living with Alzheimer’s disease globally to better understand and manage the symptoms of the disease.

This article is part of a series of profiles on the 2020 winners of the National Academy of Medicine’s Healthy Longevity Catalyst Awards — a component of the Healthy Longevity Global Competition, a multiyear, multimillion-dollar international competition seeking breakthrough innovations to improve physical, mental, and social well-being for people as they age The current application cycle has been extended and will accept applications through April 25, 2021 Apply today! Learn more about the award, the winners’ research, and ideas for promoting healthy aging here.

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