A study in mice investigates the potential of immunotherapy in treating Alzheimer’s disease.
- Around
32 million people globally have Alzheimer’s disease, with the number
expected to increase over the next 25 years.
- There
is currently no cure for Alzheimer’s disease.
- One
potential treatment area scientists have been exploring for Alzheimer’s
disease is immunotherapy.
- Researchers
from Washington University in St. Louis have designed a way to use
antibodies to restore the nervous system’s immune cells’ ability to clear
out unwanted debris that may lead to Alzheimer’s disease.
Currently, about 32 million people around the world live with Alzheimer’s disease,
the most common form of dementia. With a
growing aging population, experts expect dementia cases to spike to 152
million by 2050.
Right now, there is no cure for Alzheimer’s disease,
and medication options are limited. For this reason,
researchers have been focused on finding more ways to treat this type of dementia.
A potential
treatment area scientists have been exploring is immunotherapy — a treatment that boosts the body’s own immune response — to fight
Alzheimer’s disease.
One of the latest studies concerning the use of immunotherapy
for Alzheimer’s disease recently appeared in the journal Science
Translational Medicine.
In this study, researchers from Washington University in St.
Louis outline a way to use antibodies to
restore the nervous system’s immune cells’ ability to clear out unwanted debris
that may lead to Alzheimer’s disease.
“Currently, there is no cure for Alzheimer’s disease, and
available treatments only offer partial relief from symptoms,” Marco
Colonna, MD, Robert Rock Belliveau professor of pathology and immunology at
Washington University in St. Louis, and corresponding author of this study
explained to Medical
News Today.
“Certain monoclonal
antibodies, like lecanemab and aducanumab,
have gained FDA [Food and Drug Administration] approval for Alzheimer’s
treatment. Other monoclonal antibodies enhance microglial responses to amyloid-beta pathology
by activating the TREM2
receptor and are undergoing clinical trials,” he told us.
“However, the effectiveness of these treatments requires
further investigation,” Colonna added. “Hence, it’s crucial to explore
additional strategies that could potentially be more effective or complement
existing monoclonal antibody treatments to enhance overall efficacy.”
How immune cells in the brain may help fight dementia
For this study, researchers used a mouse model to test their
strategy, which focused on targeting proteins that regulate the activity
of microglia — a type of immune cell — in the nervous
system.
“Microglia
respond to signals from the tissue environment, both activating and
inhibitory,” Colonna explained. “Their primary role is to clear toxic
substances that build up in the brain by phagocytosis [where the cells ‘consume’ a foreign substance]. These toxins send
signals prompting microglia to engulf them.”
“Simultaneously, microglia must safeguard the brain’s healthy
components, which send signals to deter microglial activity,” he continued. “To
enhance microglial phagocytic function, we can either provide activating
stimuli or block inhibitory ones. Our strategy focuses on inhibiting receptors
that dampen microglial phagocytosis.”
Past studies have suggested that microglia may help
combat neuroinflammation and clear out the toxic accumulation
of proteins like tau and
beta-amyloid, which is associated with Alzheimer’s disease.
An antibody that may help clear toxic plaques in the brain
Colonna and his team also studied the impact of the LILRB4
receptor, located on the microglia in the brain, and how it may impact the
development of Alzheimer’s disease.
“LILRB4 is a
receptor found on brain microglia and it interacts with a fat-carrying protein
called ApoE, which is abundant in the brain and is also a part of amyloid plaques
associated with Alzheimer’s disease,” Colonna explained. “Some variants of [the
gene that expresses] ApoE in the human population increase the risk of
Alzheimer’s.”
Originally, researchers discovered high amounts of LILRB4 on
microglial surfaces in brain tissue samples from people with Alzheimer’s
disease.
The scientists then used a mouse model capable of expressing
the human LILRB4 receptor. Their experiments showed that the LILRB4 receptor
disrupted the microglia’s ability to interact with beta-amyloid plaques.
Treating the
mice with antibodies against LILRB4 resulted in lower beta-amyloid amounts in
the brain, increased microglia activity, and reversed some behavioral changes
during maze tests that the scientists had linked to beta-amyloid accumulation.
“We discovered that when ApoE binds to LILRB4, it slows down
the ability of microglia to clear amyloid plaques,” Colonna detailed.
“On the other hand, using a specific
antibody to block ApoE from binding to LILRB4 actually boosts microglia’s
ability to clear away these plaques. This suggests that treating Alzheimer’s
patients with this antibody could potentially help in removing amyloid
plaques.”– Marco Colonna, MD
“Based on our findings, we think that treating Alzheimer’s
patients with this specific monoclonal antibody could potentially help the
brain to clear amyloid plaques and other harmful proteins that build up in
neurodegenerative diseases,” he continued. “This treatment may also may be
combined with other treatments currently tested to increase their efficacy.”
Neuroimmunology: A new approach to Alzheimer’s treatment
After reviewing this study, Karen D. Sullivan,
PhD, a board-certified neuropsychologist, owner of I CARE FOR YOUR BRAIN,
and Reid Healthcare Transformation fellow at FirstHealth of the Carolinas in
Pinehurst, NC, not involved in the research, told MNT that it provides additional evidence of the
power of neuroimmunology to treat and, hopefully, ultimately
cure Alzheimer’s disease.
“These research insights provide further support that
monoclonal antibodies can interfere with the build-up of beta-amyloid, which is
considered to be one of the primary biomarkers of the disease,” Sullivan said.
“What we still
don’t know is how a reduction of amyloid from this new mechanism, anti-LILRB4
microglia signaling, benefits cognition and the course of the disease process,”
she noted.
“With the so-called ‘graying of the world,’ we are about to
hit a population explosion of people living with dementia,” Sullivan added.
“The financial and psychological toll of this significant increase in people
diagnosed with the neurodegenerative disorder is massive and we need all
resources pointed towards care and medical management of these diseases.”
Working toward more effective Alzheimer’s treatments
MNT also
spoke with Manisha Parulekar, MD, director of the Division of
Geriatrics at HackensackUMC, 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.
Like Sullivan, Parulekar was not involved in this research.
“Microglia are essential for various brain protective
functions like maintaining [the] blood-brain
barrier, which protects the brain from harmful substances like toxins,”
Parulekar explained.
“This study is
outlining [the] possible impact of disruption of these protective functions in
the etiology [causal mechanisms] of Alzheimer’s disease, and possible
interventions. We are still working towards effective treatment for
Alzheimer’s. Microglia function restoration could be a possible treatment
option,” she told us.
“Alzheimer’s disease is the most common form of dementia, affecting millions
of people worldwide,” Parulekar continued. “The number of cases is projected to
increase significantly in the coming decades due to aging populations. It is a
public health crisis worldwide, as it does put a significant financial and
caregiver burden on the family, community and society.”
The expert said we still lack an effective treatment that can
stop or reverse the disease progression.
“Our ongoing research is suggesting that Alzheimer’s disease
is possibly caused by multiple processes/risk factors,” she added. “Hence, it
is essential to explore various treatments that can stop or slow down the
neurodegenerative process.”
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