A newly identified genetic variant may reduce the risk of Alzheimer’s by up to 71%.
- Although
researchers are still unclear as to what causes Alzheimer’s disease, they
do know genetics plays a role.
- Much
recent research has revolved around the study of genetic variants and
their role in Alzheimer’s disease.
- Researchers
from Columbia University Vagelos College of Physicians and Surgeons in New
York have identified a new genetic variant that helps defend against
Alzheimer’s disease, reducing a person’s odds by up to 71%.
Researchers are still
unclear as to what really causes Alzheimer’s disease,
a type of dementia affecting
about 32 million people globally.
However, they do know
that genetics plays
a role, specifically some genetic variants, which include a mutation or change in the
DNA of a gene that causes it to act differently.
Searching and studying
genetic variants in Alzheimer’s disease is a major area of study right now. For
example, scientists have discovered that genetic variants of the APOE gene and myeloid
cells 2 (TREM2) may be tied to Alzheimer’s disease.
And a study published in March 2024 identified 17
genetic variants associated with Alzheimer’s disease in five genomic
regions.
Now, scientists from Columbia University Vagelos
College of Physicians and Surgeons in New York have identified a previously
unknown genetic variant that helps defend against Alzheimer’s disease, reducing
a person’s odds of developing this condition by up to 71%.
The study was recently
published in the journal Acta Neuropathologica.
What role
does fibronectin play in brain health?
For this study,
researchers focused on a variant that occurs in the gene that expresses fibronectin.
Fibronectin is an adhesive glycoprotein that can be found on cell surfaces and
in the blood and helps with certain cell functions.
Fibronectin can also be
found in the blood-brain
barrier, where it helps control what moves in and out of the brain.
Previous research shows that people with Alzheimer’s
disease have a higher
concentration of fibronectin in their blood compared to those who
do not.
The researchers believe
that people who have a mutation in the fibronectin gene are protected against
Alzheimer’s disease as it helps to stop the buildup of too much fibronectin in
the blood-brain barrier.
“These results gave us
the idea that a therapy targeting fibronectin and mimicking the protective
variant could provide a strong defense against the disease in people,” study
co-leader Richard Mayeux, MD, chair of neurology and the Gertrude H.
Sergievsky Professor of Neurology, Psychiatry, and Epidemiology at Columbia
University, noted in a press
release.
“We may need to
start clearing amyloid much earlier and we think that can be
done through the bloodstream,” he suggested. “That’s why we are excited about
the discovery of this variant in fibronectin, which may be a good target for
drug development.”
Gene variant
tied to 71% lower Alzheimer’s disease risk
Researchers further discovered that the protective
fibronectin gene variant occurred in people who never developed symptoms of
Alzheimer’s disease, although they had inherited the e4
form of the APOE gene, which previous
research shows significantly increases a person’s risk of developing the
disease.
Scientists analyzed the
genetic data of several hundred people over the age of 70 who were also
carrying the APOEe4 gene variant. Study participants were
from various ethnic backgrounds and some did have Alzheimer’s disease.
After combining their
study results with those from replicated studies conducted at Stanford and
Washington Universities, researchers found the fibronectin gene variant lowered
Alzheimer’s disease risk by 71% in people carrying the APOEe4 gene
variant.
In the same press
release cited above, Caghan Kizil, PhD, associate professor of neurological
sciences at Columbia University Vagelos College of Physicians and Surgeons and
co-leader of the study, explained:
“Alzheimer’s
disease may get started with amyloid deposits in the brain, but the disease
manifestations are the result of changes that happen after the deposits appear.
Our findings suggest that some of these changes occur in the brain’s
vasculature and that we may be able to develop new types of therapies that
mimic the gene’s protective effect to prevent or treat the disease.”
“There’s a significant
difference in fibronectin levels in the blood-brain barrier between cognitively
healthy individuals and those with Alzheimer’s disease, independent of
their APOEe4 status,” Kizil added.
“Anything that reduces
excess fibronectin should provide some protection, and a drug that does this
could be a significant step forward in the fight against this debilitating
condition,” he suggested.
Findings may
eventually lead to new Alzheimer’s treatments
After reviewing this
study, Karen
D. Sullivan, PhD, ABPP, a board-certified neuropsychologist, owner of I
CARE FOR YOUR BRAIN, and Reid Healthcare Transformation Fellow at FirstHealth
of the Carolinas in Pinehurst, NC, told Medical News Today she
was very excited about this study and its potential.
“This research provides
strong evidence that the fibronectin variant may be a novel therapeutic target
in Alzheimer’s disease,” Sullivan told us.
“Even though we do have
FDA-approved disease-modifying drugs for Alzheimer’s disease now with lecanemab (Leqembi),
they aren’t anywhere near as powerful as we need,“ she pointed out.
“We need an agent that intervenes in the earliest
stages of amyloid accumulation and I’m hopeful they are onto something with
this insight. It’s exciting to think the protective effects of this gene [have]
been shown to be effective in two animal models and in a population-wide human
study,” Sullivant said.
“We need to study the
people with the fibronectin genetic variant in more detail and understand how
this genetic variant expresses itself phenotypically,” she added.
Genes may
influence blood-brain barrier disruption in dementia
MNT also spoke with Manisha Parulekar, MD, director of the Division of
Geriatrics at Hackensack University Medical Center, and co-director of the
Center for Memory Loss and Brain Health and associate professor at the
Hackensack Meridian School of Medicine in New Jersey, about this study.
Parulekar commented that
any new discovery that may reduce the odds of developing Alzheimer’s disease is
very exciting and encouraging.
“While the exact cause
of Alzheimer’s disease remains unknown, several factors are believed to
contribute to its development, including the accumulation of amyloid plaques
and tau
tangles in the brain, as well as vascular dysfunction,” she detailed.
“APOE4 has
been linked to increased risk of Alzheimer’s but [the] exact mechanism on why
some people with this gene do not get Alzheimer’s is not known,” said
Parulekar.
What we do know, she added,
is “that the blood-brain barrier plays a crucial role in maintaining the health
and function of the brain.”
“This study is suggesting a possible mechanism for
the disruption of the blood-brain barrier, and a pathway to prevent or correct
this disruption. It is exciting that we are looking at multiple pathways for
the etiology of Alzheimer’s. It will be helpful to get confirmation of these
findings and applications in finding potential cure or prevention of this
debilitating disease,” Parulekar told us.
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