Researchers at the University of Colorado Anschutz find that the overexpression of a gene improves learning and memory in Alzheimer’s disease.
According to a recent study by researchers at the University of Colorado Anschutz Medical Campus, the overexpression of a gene linked to cell division and the structure and function of neurons may prevent and protect against cognitive decline in both mice and humans with Alzheimer’s disease (AD).
This happens despite the presence of amyloid beta (Abeta), the main component of plaques in the brains of patients with Alzheimer’s disease. In the past, scientists have focused on the plaques while seeking treatments for the deadly condition. In this instance, they went around them.
The findings were recently published in the journal iScience.
“Overexpressing KIF11 in mice did not affect the amyloid levels in the brain,” said the study’s co-senior author Huntington Potter, Ph.D., professor of neurology and director of the University of Colorado Alzheimer’s and Cognition Center and of Alzheimer’s research at the Linda Crnic Institute for Down Syndrome at the University of Colorado School of Medicine. “Yet they were still cognitively normal despite the plaques. This is one of the best indications that you can maintain cognition without getting rid of the plaques.”
KIF11 is a motor protein best known for its involvement in non-neuronal cells’ mitosis or cell division. However, it also has a significant role in how neurons develop their dendrites and dendritic spines, which are essential for learning and memory and serve as a means of communication between neurons. However, Abeta, the primary component of Alzheimer’s plaques, has the ability to block KIF11 and damage these structures.
The researchers found that overexpressing the gene in mice with AD led to improved performance on cognitive tests compared to AD mice with normal levels of KIF11. Then they analyzed genetic data from human AD patients provided by the Religious Orders Study and the Rush Memory and Aging Project (ROS/MAP) at Rush University in Chicago. They wanted to know if naturally occurring variations in KIF11 levels correlated with better cognitive performance in adults with or without amyloid plaques.
“Our results from analyzing the human data indicate that higher levels of KIF11 correlate with better cognitive performance in a cohort of older adults with amyloid pathology,” said the study’s lead author Esteban Lucero, Ph.D., from the University of Colorado School of Medicine.
“Thus, our results suggest that higher KIF11 expression levels may partially prevent cognitive loss during the course of AD in humans, which aligns with our findings regarding the role of KIF11 in animal models of AD,” Lucero said.
Potter and co-senior author Heidi Chial, Ph.D., assistant professor of neurology and director of grant strategy and development at the University of Colorado Alzheimer’s and Cognition Center, said this information paves the way for researchers to begin testing new or existing drugs that can safely create this effect in humans.
“Many current experimental treatments for AD have focused on reducing Abeta production or on increasing the clearance of Abeta plaques,” Chial said. “Most of these approaches have failed to prevent or reverse cognitive decline in clinical trials. Clearly, alternative approaches to the development of AD therapeutics are needed.”
Reference: “Increased KIF11/kinesin-5 expression offsets Alzheimer Aβ-mediated toxicity and cognitive dysfunction” by Esteban M. Lucero, Ronald K. Freund, Alexandra Smith, Noah R. Johnson, Breanna Dooling, Emily Sullivan, Olga Prikhodko, Md. Mahiuddin Ahmed, David A. Bennett, Timothy J. Hohman, Mark L. Dell’Acqua, Heidi J. Chial and Huntington Potter, 7 October 2022, iScience.
The study was funded by the National Institutes of Health, the Global Down Syndrome Foundation, and private philanthropists.
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