Groundbreaking therapy reduces Alzheimer’s disease effects by 80%
[Apr. 20, 2023: Staff Writer, The Brighter Side of News]
A novel, disease-modifying therapy for Alzheimer’s disease may involve the whole exchange of blood. (CREDIT: Creative Commons)
In a groundbreaking study published in Molecular Psychiatry, a team of researchers from the University of Texas Health Science Center at Houston (UTHealth Houston) has discovered a novel therapy for Alzheimer’s disease that involves a whole exchange of blood.
The study showed that this treatment effectively decreased the formation of amyloid plaque in the brains of mice, which is considered a central player in Alzheimer’s disease pathology. This innovative approach could hold the key to revolutionizing Alzheimer’s disease treatment, which has long been a challenging area for researchers.
The research team was led by senior author Claudio Soto, PhD, professor in the Department of Neurology with McGovern Medical School at UTHealth Houston, in collaboration with first author Akihiko Urayama, PhD, associate professor in the department.
They performed a series of whole blood exchange treatments on mice exhibiting Alzheimer’s disease-causing amyloid precursor proteins with complete blood from healthy mice of the same genetic background. The results were remarkable: after multiple blood transfusions, the researchers found that the development of cerebral amyloid plaques in a transgenic mice model of Alzheimer’s disease was reduced by 40% to 80%. This reduction also resulted in improved spatial memory performance in aged mice with the amyloid pathology, and lowered the rates of plaque growth over time.
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“This article provides a proof-of-concept for the utilization of technologies commonly used in medical practice, such as plasmapheresis or blood dialysis, to ‘clean’ blood from Alzheimer’s patients, reducing the buildup of toxic substances in the brain,” said Soto, director of the George and Cynthia Mitchell Center for Alzheimer’s Disease and Related Brain Disorders and the Huffington Foundation Distinguished Chair in Neurology at McGovern Medical School. “This approach has the advantage that the disease can be treated in the circulation instead of in the brain.”
The treatment of Alzheimer’s disease has been complicated due to the difficulty in delivering therapeutic agents across the blood-brain barrier. However, through their latest research, Urayama, Soto, and others discovered that manipulating circulating components in Alzheimer’s disease could be the key to solving this issue.
Previous studies by Soto and other UTHealth Houston researchers have shown that the misfolding, aggregation, and buildup of amyloid beta proteins in the brain plays a central role in Alzheimer’s disease. Therefore, preventing and removing misfolded protein aggregates is considered a promising treatment for the disease.
A team led by Claudio Soto, PhD, performed a series of whole blood exchange treatments to partially replace blood from mice with Alzheimer’s disease-causing amyloids in their brains with blood from healthy mice. (CREDIT: UTHealth Houston)
“Blood vessels in the brain are classically considered the most impermeable barrier in the body,” Urayama said. “We have been aware that the barrier is at the same time a very specialized interface between the brain and the systemic circulation.”
While the exact mechanism by which this blood exchange reduces amyloid pathology and improves memory is currently unknown, there are multiple possibilities. One possible explanation is that lowering amyloid beta proteins in the bloodstream may help facilitate the redistribution of the peptide from the brain to the periphery.
Another theory is that blood exchange somehow prevents amyloid beta influx or inhibits the re-uptake of cleared amyloid beta, among other potential explanations.
Schematic representation of the sites used for blood exchange along the jugular brain. C: Simulation curves to estimate the percentage of blood replacement considering the bodyweight of animals and the volume of blood withdrawal. (CREDIT: UTHealth Houston)
The study’s implications are significant: a target for Alzheimer’s disease therapy may lie in the periphery, rather than the brain. The blood exchange treatment can effectively remove toxic substances from the bloodstream, reducing the buildup of amyloid plaque in the brain. It could also pave the way for the development of new therapies that can treat Alzheimer’s disease in the circulation, rather than in the brain.
“Alzheimer’s disease affects millions of people worldwide, and current therapies are limited in their efficacy,” Soto said. “Our study offers a new approach that could provide a breakthrough in the treatment of Alzheimer’s disease.”
Blood exchange treatment scheme. A: Schematic representation of blood withdrawal and infusion procedure. In Tg2576 mice at the age of 3 through 17 months. (CREDIT: UTHealth Houston)
The blood exchange therapy used in the study is based on plasmapheresis, a medical procedure that involves removing blood plasma from the body and replacing it with a substitute solution. This technique has been used for many years to treat various medical conditions, such as autoimmune disorders and certain types of poisoning.
In the case of Alzheimer's disease, plasmapheresis could potentially remove toxic substances from the bloodstream that contribute to the formation of amyloid plaques in the brain. This is significant because amyloid plaques are a hallmark of Alzheimer's disease and are believed to be a major contributor to cognitive decline in affected individuals.
The study conducted by the UTHealth Houston research team provides preliminary evidence that this approach could be effective in reducing the formation of amyloid plaques in the brains of mice with Alzheimer's disease. However, more research is needed to determine whether this therapy is safe and effective in humans.
Blood exchange treatment decreases the accumulation of cerebral amyloid plaques. (CREDIT: Molecular Psychiatry)
The researchers also noted that this approach may have some advantages over traditional drug-based therapies for Alzheimer's disease. For example, the blood exchange therapy could be delivered via intravenous infusion, which is less invasive than some other treatment approaches. Additionally, it may be easier to deliver the therapy to a larger population of individuals with Alzheimer's disease, as the procedure is already widely used in medical practice.
Despite the potential benefits of this approach, there are also some potential drawbacks. For example, plasmapheresis can be a costly and time-consuming procedure, which could limit its accessibility for some individuals. Additionally, the long-term effects of repeated blood exchange treatments on the body are not well understood and would need to be further explored.
Despite these limitations, the findings of the study offer hope for the development of new and innovative treatments for Alzheimer's disease. As the population ages and the prevalence of this devastating disease continues to grow, new approaches are urgently needed to address this major public health challenge.
For more science news stories check out our New Discoveries section at The Brighter Side of News.
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