Genes involved in neuronal structure and function may prevent Alzheimer's disease

Overexpression of a gene related to cell division, neuronal structure and function may prevent and protect against cognitive decline
in mice and humans with Alzheimer's disease (AD), according to a new study by scientists.
University of Colorado Anschutz Medical Campus

News on October 25

Despite the presence of β-amyloid (Aβ), the main component of plaque in the brains of AD patients, a gene called Kinesin-5 or KIF11 can still do this
.
Traditionally, scientists have targeted these plaques
when looking for a cure for this deadly disease.
In this case, they bypassed the plaques
.
The study was recently published in the journal iScience
, a subsidiary of Cell.

The study was published on October 7, 2022 in the journal iScience (latest impact factor: 6.
107).

"Overexpression of KIF11 in mice does not affect amyloid levels in the brain," said
Dr.
Huntington Potter, co-senior author of the study 。 He is a professor of neurology, director of the Alzheimer's Disease and Cognition Center at the University of Colorado, and director of Alzheimer's research at the Linda Crnic Down Syndrome Institute at the University of Colorado School of Medicine.

This is one of the best signs that you can maintain cognitive performance
without removing the plaque.
”

KIF11 is a motor protein widely known
for its role in mitosis, or cell division, in non-neuronal cells.
But it also plays a vital role
in the formation of dendrites and dendritic spines of neurons.
Dendrites and dendritic spines are used to communicate with other neurons and are important
for learning and memory.
However, Aβ, the main component of Alzheimer's plaque, can inhibit KIF11 and cause damage
to these structures.

The researchers found that AD mice that overexpressed 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 Orders Study (ROS) and the Rush Aging Project (MAP) at Chicago Rush University.
They wanted to know if natural changes in KIF11 levels were associated with
better cognitive performance in adults with or without amyloid plaques.

The results of our analysis of human data suggest that higher levels of KIF11 are associated with better cognitive performance in the amyloid pathologically positive cohort of older adults," said
lead author Esteban Lucero, Ph.
D.
, from the University of Colorado School of Medicine.

"Therefore, our results suggest that higher levels of KIF11 expression may protect against cognitive loss during human AD to some extent, consistent with
our findings on the role of KIF11 in animal models of AD," Lucero said.
”

Potter and Dr.
Heidi Chial, 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 this 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 focus on reducing Aβ production or increasing the clearance of Aβ plaques," Chial said, "and most of these approaches have failed to prevent or reverse cognitive decline
in clinical trials.
" Clearly, the development of alternative approaches to AD therapy is necessary
.
”