Kinesin-5 Gene May Protect Against Alzheimer’s Disease

According to a new study, cognitive decline in both mice and humans with Alzheimer’s disease (AD) may be protected by the overexpression of a gene linked to cell division and the structure and function of neurons.

The gene Kinesin-5 or KIF11 accomplishes this despite the fact that amyloid beta, the main component of plaques in the brains of those with AD, is present. In the past, scientists have mainly focused on the plaques when trying to find a cure for the disease. They bypassed the plaques in this instance.

“Overexpressing KIF11 in mice did not affect the amyloid levels in the brain. 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,”

said the study’s co-senior author, Huntington Potter, Ph.D.. Potter is 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.

Variations In Kinesin-5 Levels

kinesin-5 alzheimers study graphical abstract
Credit: iScience (2022). DOI: 10.1016/j.isci.2022.105288

The motor protein Kinesin-5 is most well-known for its function in non-neuronal cells’ mitosis or cell division. However, it also significantly impacts the development of neurons’ dendrites and dendritic spines, which are vital for learning and memory and are used for communication with other neurons. But Amyloid beta, the primary component of Alzheimer’s plaques, has the ability to inhibit KIF11 and harm these structures.

In comparison to AD mice with normal levels of KIF11 (Kinesin-5), the researchers discovered that overexpressing the gene in AD mice resulted in improved performance on cognitive tests.

Then they examined genetic information from AD patients who had been a part of Rush University’s Religious Orders Study and Memory and Aging Project (ROS/MAP) in Chicago. Researchers wanted to find out if there was a link between natural changes in KIF11 levels and better cognitive function in adults with or without amyloid plaques.

Cognitive Decline Protection

Higher levels of KIF11 are correlated with better cognitive performance in an older adult cohort with amyloid pathology, according to results from human data analysis.

The study’s findings, consistent with the findings regarding KIF11’s function in animal models of AD, suggest that higher KIF11 expression levels may partially prevent cognitive decline during the course of Alzheimer’s disease in humans.

This knowledge paves the way for researchers to start testing new or existing drugs that can safely produce this effect in humans, according to 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.

“Many current experimental treatments for AD have focused on reducing Abeta production or on increasing the clearance of Abeta plaques. 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,”

Chial said.

Reference:

Esteban M. Lucero et al, Increased KIF11/kinesin-5 expression offsets Alzheimer Aβ-mediated toxicity and cognitive dysfunction, Science Volume 25, Issue 11, 105288