The main neuropathological changes in Alzheimer’s disease are neuronal death, synaptic alterations, brain inflammation, and cerebral protein aggregates in the form of amyloid plaques and neurofibrillary tangles. Compelling evidence suggests that the misfolding, aggregation and cerebral deposition of amyloid-beta (Aβ) plays a central role in the disease. Thus, the prevention and removal of misfolded protein aggregates are considered a promising strategy for treating AD.
A new study from UTHealth Houston offers a novel, disease-modifying therapy for Alzheimer’s. It involved a whole exchange of blood. The scientists suggested that the entire exchange of blood could effectively diminish the formation of amyloid plaque in the brains of mice.
Senior author Claudio Soto, Ph.D., professor in the Department of Neurology with McGovern Medical School at UTHealth Houston, said, “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. This approach has the advantage that the disease can be treated in the circulation instead of in the brain.”
“Blood vessels in the brain are classically considered the most impermeable barrier in the body. We know the barrier is simultaneously a very specialized interface between the brain and the systemic circulation.”
According to scientists, the formation of brain amyloid plaques in a transgenic mouse model of Alzheimer’s disease was reduced by 40% to 80% following numerous blood transfusions. In older animals with amyloid disease, this lowering also improved spatial memory ability and slowed plaque growth rates.
However, the exact mechanism through 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 prevents amyloid beta influx or inhibits the re-uptake of cleared amyloid beta, among other potential explanations.
However, regardless of the mechanisms of action associated with the blood exchange treatment, the study shows that a target for Alzheimer’s disease therapy may lie in the periphery.