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Are Memory Loss in Alzheimer’s Disease Related to Changes in Blood Vessels in the Brain?
Alzheimer’s disease is recognized as a brain cell disease that is known to be associated with β-amyloid plaque deposition. Its association with cerebral blood vessels has also been gaining attention in recent years. In a newly published study in the Proceedings of the National Academy of Sciences, a team of U.S. researchers revealed previously unknown changes in cerebral blood vessels, providing a breakthrough in the understanding of Alzheimer’s disease and a new entry point for the development of new drugs.
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Constriction of the Pial Arteries Due to the Accumulation of Aβ1-40
The pathogenesis of Alzheimer’s disease remains unknown, but there is growing evidence that the blood supply to the brain is also affected in the process. Researchers at the University of Manchester have found that this phenomenon may be related to the accumulation of the β-amyloid (1–40) peptide (Aβ1-40) in the walls of small arteries.
The surface of the brain is covered with small arteries called pial arteries, which control the supply of blood and oxygen to the brain. Once these arteries are narrowed for some reason and blood flow is reduced for a long time, the brain will not be able to receive sufficient nutrients. This is one of the reasons why Alzheimer’s patients experience memory loss.
In experiments with mice, when researchers examined the pial arteries of aged mice with excessive production of Aβ1-40 due to Alzheimer’s disease, they found that these arteries were significantly narrower compared to healthy mice. They also noticed that the narrowing of these arteries was mainly due to decrease in the activity of transmembrane proteins called large-conductance Ca2+-activated K+ channels (BK channels), which send out signals to make the arteries wider when functioning properly. It was found that Aβ1-40 was responsible for the blockage of BK channels, probably resulting in constriction of pial arteries.
In order to confirm whether Aβ1-40 was blocking BK channels from working properly, the team allowed exposure of cerebral arteries from young, healthy wild-type mice to Aβ1-40 peptides and measured the signals generated by BK proteins an hour later. The results showed that Aβ1-40 actually attenuated these signals and caused the arterial constriction.
Will the Research Lead to a New Treatment for Alzheimer’s Disease?
The researchers plan to further investigate how Aβ1-40 blocks BK channels so that they can develop and test drugs in an attempt to improve cerebrovascular functions impaired by the disease, thereby slowing the memory loss caused by the progression of Alzheimer’s disease.
Dr. Adam Greenstein, principal investigator and Clinical Senior Lecturer in the Division of Cardiovascular Sciences at the University of Manchester, pointed out that much of the previous studies related to Alzheimer’s disease have focused on the cerebral nerves, but none of the more than 500 drugs that have been tested to date for Alzheimer’s disease have shown any successful results.
The team believes that this study is a significant step forward in understanding Alzheimer’s disease. In addition to showing how Alzheimer’s disease affects small blood vessels, it also opens the door to new research to find effective treatments for the disease.
According to the WHO, more than 55 million people worldwide are currently suffering from dementia, with Alzheimer’s disease likely to account for nearly 70% of these cases. The number is expected to continue to rise in the wake of population aging. Professor Metin Avkiran, Associate Medical Director of the British Heart Foundation, stated that this discovery may bring about a much needed treatment for this devastating disease.
Written by Nana Ho
Translated by Richard Chau