Can we leverage immunotherapy against 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.
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.” - Source: MedicalNewsToday
Did you know?
Alzheimer’s
It is a public health crisis worldwide, as it does put a significant financial and caregiver burden on the family, community and society.”
STATS
Immunotherapy can empower your immune system against cancer
1891: Dr. William B. Coley—CRI’s “grandfather”—uses first immunotherapy to save a patient with inoperable cancer.
There are currently five different classes of immunotherapies available for patients, for over 20 cancer types.
Over 100 billion immune cells are produced every day in a person’s bone marrow.
Macrophages—literally the “big eaters” of the immune system—can devour cancer cells.
B cells can create trillions of unique antibodies that provide precision targeting.