Altering Brain Chemistry Through Exercise can Help to Protect Aging Synapses

It has been discovered, with a recent UC San Francisco study, that when elderly people stay active, their brains have more of a class of proteins that enhances the connections between neurons maintaining healthy cognition; even in people whose brains at autopsy were riddled with toxic proteins associated with Alzheimer’s and other neurodegenerative diseases.

“Our work is the first that uses human data to show that synaptic protein regulation is related to physical activity and may drive the beneficial cognitive outcomes we see,” said Kaitlin Casaletto, PhD, an assistant professor of neurology and lead author on the study, which appears in the January 7 issue of Alzheimer’s & Dementia: The Journal of the Alzheimer's Association. “Maintaining the integrity of these connections between neurons may be vital to fending off dementia since the synapse is really the site where cognition happens,” went on “physical activity—a readily available tool—may help boost this synaptic functioning.”

Casaletto, a neuropsychologist and member of the Weill Institute for Neurosciences, worked with William Honer, MD, a professor of psychiatry at the University of British Columbia and senior author of the study, to leverage data from the Memory and Aging Project at Rush University in Chicago. 

Casaletto and Honer found that elderly people who remained active had higher levels of proteins that facilitate the exchange of information between neurons. This result supported Honer’s earlier findings from his previous study that people who had more of these proteins in their brains when they died were better able to maintain their cognition late in life. Honer’s previous study incorporated the documenting of late-life physical activity of elderly participants, who also agreed to donate their brains when they died.

To their surprise, Honer said, “the researchers found that the effects ranged beyond the hippocampus, the brain’s seat of memory, to encompass other brain regions associated with cognitive function. It may be that physical activity exerts a global sustaining effect, supporting and stimulating the healthy function of proteins that facilitate synaptic transmission throughout the brain.” 

The hallmarks of Alzheimer’s disease are the accumulation of amyloid and tau within the brain. Many scientists believe amyloid accumulates first, then tau, causing synapses and neurons to degrade and subsequently fall apart.

“In older adults with higher levels of the proteins associated with synaptic integrity, this cascade of neurotoxicity that leads to Alzheimer’s disease appears to be attenuated. Taken together, these two studies show the potential importance of maintaining synaptic health to support the brain against Alzheimer’s disease,” Casaletto explained.

Casaletto, K, Ramos-Miguel, A, VandeBunte, A, et al. Late-life physical activity relates to brain tissue synaptic integrity markers in older adults. Alzheimer's Dement. 2021; 1- 13.


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