Research Holds Promise for Treating Cognitive Decline

A recently discovered genetic variation holds promise for treating age-related cognitive decline. Neuroscientist Dena Dubal confers with colleagues on progress in the lab. Photo by Steve Babuljak.

A recently discovered genetic variation holds promise for treating age-related cognitive decline. Neuroscientist Dena Dubal confers with colleagues on progress in the lab. Photo by Steve Babuljak.

As the oldest of the 76.4 million baby boomers in the US stare down old age, cognitive decline will be on a steady incline. However, genetics dealt a select few a protein-rich hand. The luckiest among them carry a variant of the klotho gene, which enhances learning and memory over the lifetime.

As the world's population ages, cognitive frailty is our biggest biomedical challenge.

DENA DUBAL, MD, PhD, David A. Coulter Endowed Chair in Aging and Neurodegeneration

Fueled by an endowed chair gifted by David and Susan Coulter, UCSF neurologist Dena Dubal co-led a team in investigating how klotho affects brain function. Dubal and her colleagues were the first to show that people who carry a single copy of the KL-VS variant of the klotho gene perform better on a wide variety of cognitive tests. When modeling the effects in mice, Dubal found that the variant strengthened connections between neurons that make learning possible by increasing the action of a cell receptor critical to forming memories.

Dubal also found that people with the variant have larger dorsolateral prefrontal cortexes, the area of the brain that is responsible for planning and decision making. Her work has remarkable implications for treating age-related diseases like Alzheimer’s.

“Philanthropy has played a defining role in the discoveries made in the last three years by my very new and young lab,” says Dubal. “I would not have the resources to lead my lab without David and Susan Coulter’s support, period.”

A recently discovered genetic variation holds promise for treating age-related cognitive decline. Neuroscientist Dena Dubal confers with colleagues on progress in the lab. Photo by Steve Babuljak.

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