New research into Alzheimer’s disease (AD) treatment by a team led by Claudio Soto, PhD, professor in the Department of Neurology with McGovern Medical School at UTHealth Houston has shown in a mouse study that a whole exchange of blood decreased the formation in the brain of amyloid plaque.
The research team, which also included Akihiko Urayama, PhD, associate professor of UTHealth, conducted a series of whole blood exchanges which partially replaced the blood in mice that exhibited AD-causing amyloid precursor proteins with complete blood from healthy mice of the same genetic background. Results of their work were published today in the journal Molecular Psychiatry.
“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, lead author of the paper and director of the George and Cynthia Mitchell Center for Alzheimer’s Disease and Related Brain Disorders. “This approach has the advantage that the disease can be treated in the circulation instead of in the brain.”
The treatment of AD has long proven to be difficult due to the challenges of designing treatments that can cross the blood-brain barrier. Soto and others at UT Health have shown, as has other researcher in the area, that the misfolding, aggregation and buildup of amyloid proteins play a significant role in the development and the advancement of AD.
“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.”
The premise of this latest research is straightforward: if amyloid plaque is central to disease development, reducing or eliminating the presence of plaque should at least slow disease progression. In their experiment replacing the blood of transgenic mice showing early sings of AD development with that of healthy mice, the researchers showed amyloid plaque reductions of between 40% and 80%. In addition, aged with mice amyloid pathology exhibited improved spatial memory performance as well as lowered rates of plaque growth over time.
The researchers noted that these early studies still leave some questions unanswered that could be addressed by future research. Among the most pressing question is finding the exact mechanism by which whole blood exchange reduces amyloid pathology and improves memory. One possibility noted by the team is that lowering amyloid beta proteins in the bloodstream may help facilitate their redistribution 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. Regardless, this new research shows significant progress in a potentially new therapeutic area for the disease.
“Our results suggest that a target for AD therapy may exist in the peripheral circulation, which could open a novel disease-modifying intervention for AD,” the researchers wrote.
