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TGen, Northwestern University study of ‘SuperAgers’ offers genetic clues to their cognitive performance

MAP2K3 genetic variants could help slow age-related memory loss

PHOENIX, Ariz., and CHICAGO, Ill. — May 29, 2018 — All humans experience some cognitive decline as they age. But how is it that some people in their 80s and beyond still have the memory capacity of those 30 or more years younger?

Recent studies have shown that these SuperAgers have less evidence of brain atrophy, have thicker parts of the brain related to memory, and lower prevalence of the pathological changes associated with Alzheimer’s disease.

Now, a study by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, and Northwestern University Feinberg School of Medicine suggests that having resilient memory performance during aging could be inherited, and that a particular gene might be associated with SuperAgers.

The study results, published today in the journal Frontiers in Aging Neuroscience, suggest that therapies targeting the MAP2K3 gene could reduce age-related memory decline, and perhaps the threat of memory loss posed by Alzheimer’s disease.

“This study suggests that SuperAgers may have a genetic ‘leg up’ on the normal aging population — they may have higher resistance to age-related cognitive changes — and also that this might highlight a new way to enhance memory performance,” said Dr. Matt Huentelman, Ph.D., TGen Professor of Neurogenomics, and the study’s lead author.

Researchers sequenced the genomes of 56 SuperAgers in the hunt for genetic variations. They defined SuperAgers as those individuals 80 years or older who scored at or above average normative values for adults age 50-65 in episodic memory tests, and at least average-for-age in other cognitive tests.

They compared these to a control group of 22 cognitively average individuals, those who scored within the average-for-age on episodic memory and other cognitive tests, as well as with a large group of individuals from the general population.

They found that the SuperAgers were enriched for genetic changes in the MAP2K3 gene compared to the two control groups.

“Based on our findings, we postulate MAP2K3 inhibitors may represent a novel therapeutic strategy for enhanced cognition and resistance to Alzheimer’s disease,” said Dr. Emily J. Rogalski, Ph.D., Associate Professor at the Mesulam Cognitive Neurology and Alzheimer’s Disease Center at Northwestern’s Feinberg School of Medicine, and the study’s senior author. “Replication of the finding and mechanistic studies are important next steps.”

This study — Associations of MAP2K3 gene variants with superior memory in SuperAgers — was funded in part by the National Institutes of Health, the National Institute on Aging (grant numbers R01 AG045571 and P30 AG13854), and the Davee Foundation. Tissue samples were provided by the National Cell Repository for Alzheimer’s Disease. Data collection and sharing was provided by the Alzheimer’s Disease Neuroimaging Initiative.

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About TGen
Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. TGen is focused on helping patients with neurological disorders, cancer, diabetes, and infectious diseases, through cutting edge translational research (the process of rapidly moving research towards patient benefit).  TGen physicians and scientists work to unravel the genetic components of both common and rare complex diseases in adults and children. Working with collaborators in the scientific and medical communities literally worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. TGen is affiliated with City of Hope, a world-renowned independent research and cancer and diabetes treatment center: www.cityofhope.org. This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. For more information, visit: www.tgen.org. Follow TGen on FacebookLinkedIn and Twitter @TGen.

Media Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]

About Northwestern University Feinberg School of Medicine
Northwestern University Feinberg School of Medicine is a top 20 medical school where nationally recognized scientists collaborate with skilled clinicians to improve human health. More than 3,400 faculty members teach, practice medicine, and conduct research at the medical school, which is a central component of Northwestern Medicine, a premier academic health system.


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