AULORA, Colorado (Oct.
25, 2022) — Overexpression of a gene associated with cell division and neuronal structure and function may prevent and protect cognitive decline
in mice and humans with Alzheimer's disease (AD), according to a new study by scientists at the University of Colorado's Anschutz School of Medicine.
The gene, called Kinesin-5 or KIF11, is able to do this
despite the presence of β amyloid (Abeta), which is the main component of plaque in the brains of AD patients.
Traditionally, scientists have targeted these plaques
when looking for a cure for this deadly disease.
In this case, they bypassed them
.
The study was published last week on the website
of the journal iScience.
"Overexpression of KIF11 in mice does not affect amyloid levels in the brain," said
Huntington Porter, Ph.
D.
, co-senior author of the study.
He is a professor of neurology and director of the Alzheimer's Center for Disease and Cognition at the University of Colorado and director
of Alzheimer's Research at the Linda Kernick Down Syndrome Institute at the University of Colorado School of Medicine.
"Despite the plaque, their cognitive abilities remained normal
.
This is one of the best signs that you can maintain your cognitive abilities
without removing the plaque.
”
KIF11 is a motor protein known for
its role in non-neuronal cell mitosis, or cell division.
But it also plays a vital role
in the formation of dendritic and dendritic spines of neurons.
Dendritic and dendritic spines are used to communicate with other neurons and are important
for learning and memory.
However, Abeta, the main component of Alzheimer's plaques, can inhibit KIF11 and cause damage to
these structures.
The researchers found that AD mice overexpressing the gene performed better
on cognitive tests compared to AD mice with normal KIF11 levels.
They then analyzed genetic data
from human AD patients provided by the Religious Order Research and Rush Memory and Aging Project (ROS/MAP) at Rush University in Chicago.
They wanted to know if natural changes in KIF11 levels were associated
with better cognitive performance in adults with or without amyloid plaques.
"Our results from analyzing human data suggest that higher levels of KIF11 are associated with better cognitive performance in older cohorts of amyloid pathology," said
study lead author Dr.
Esteban Lucero from the University of Colorado School of Medicine.
"Therefore, our findings suggest that higher levels of KIF11 expression may protect against cognitive loss in the human AD process to some extent, consistent
with our findings on the role of KIF11 in animal models of AD," Lucero said.
Porter and Dr.
Heidi Chir, assistant professor of neurology and director of grant strategy and development at the University of Colorado's Alzheimer's Center for Disease and Cognition, said the information paves the way
for researchers to begin testing new or existing drugs that can safely produce this effect in humans.
"Many current experimental treatments for AD are focused on reducing Abeta production or increasing the clearance of Abeta plaques," Kyle said
.
"In clinical trials, most of these approaches have failed to stop or reverse cognitive decline
.
Clearly, the development of alternative approaches to AD therapy is necessary
.
”
The research was supported
by the National Institutes of Health, the Global Down Syndrome Foundation, and private philanthropists.
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