Alzheimer’s diseaseConsidered to be a disease of brain cells, in addition to being known to be associated with β-amyloid (β-amyloid) plaque deposition, the association with cerebral blood vessels has also begun to attract attention in recent years.
In a new study published in the Proceedings of the National Academy of Sciences, a U.S. research team revealed previously unknown changes in blood vessels in the brain, leading to a breakthrough in the understanding of Alzheimer’s disease and the development of new drugs Offers a whole new angle of entry.
New discovery of Alzheimer’s disease research paradigm (Geneline Online International Edition)
Aβ1-40 accumulation leads to narrowing of leptomeningeal arteries
The pathological cause of Alzheimer’s disease is still unknown, but there is growing evidence that the blood supply to the brain is also affected in the process, and researchers at the University of Manchester have found that this phenomenon may be related to beta- An isoform of amyloid, Aβ1-40, is associated with accumulation in the walls of arterioles.
The surface of the brain is covered with small arteries called pial arteries, which control the blood and oxygen supply to the brain. Once these arteries narrow for a long time and reduce blood flow for some reason, the brain cannot get enough nutrients. This is one of the reasons why people with Alzheimer’s disease experience memory loss.
In experiments with mice, when the researchers looked at pial arteries in aged mice that had excess Aβ1-40 production due to Alzheimer’s disease, they found that these arteries were significantly narrower than those in healthy mice. The researchers noticed that the main reason for the narrowing of blood vessels is that Aβ1-40 turns off a protein called BK in the cells lining blood vessels, which when functioning normally, sends a signal to widen the arteries.
To determine that Aβ1-40 was blocking BK from working properly, the team soaked pial arteries from young, healthy mice in Aβ1-40 and measured the signal from the BK protein an hour later. The results showed that Aβ1-40 did attenuate these signals and cause the arteries to narrow.
Will research lead to new treatments for Alzheimer’s?
The researchers plan to further investigate how Aβ1-40 blocks the BK protein, so that researchers can develop and test drugs that seek to improve the function of brain blood vessels damaged by the disease, thereby slowing the memory loss caused by the progression of Alzheimer’s disease. .
Lead researcher Dr Adam Greenstein, Senior Clinical Lecturer in Cardiovascular Sciences at the University of Manchester, pointed out that in the past research related to Alzheimer’s disease has mostly focused on the nerves in the brain, but so far more than 500 drugs have been tried to treat Alzheimer’s disease. None of the drugs has shown successful results so far.
The research team believes that this study is an important step in understanding Alzheimer’s disease. In addition to showing how Alzheimer’s affects small blood vessels, it also opens the door to new research into finding effective treatments for Alzheimer’s.
According to WHO statistics, more than 55 million people worldwide are currently suffering from dementia, of which Alzheimer’s disease may be responsible for nearly 70% of the cases. The numbers are expected to continue to rise as the population ages. Professor Metin Avkiran, deputy medical director of the British Heart Foundation, said the discovery could lead to a much-needed treatment for this devastating disease.
References:
1. PNAS, 2022, https://doi.org/10.1073/pnas.2204581119
2. https://www.manchester.ac.uk/discover/news/blood-vessel-breakthrough-major-step-towards-alzheimers-treatment/
3. https://www.who.int/news-room/fact-sheets/detail/dementia
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