Tuesday, September 27

A new finding could lead to the creation of medicines that stop Alzheimer’s disease.

. Earlier this year, we announced that a blood test may be able to diagnose Alzheimer’s disease with 93% accuracy. Alzheimer’s disease can now be diagnosed in a single scan, according to a new approach we reported just a week ago.

A protein known as Amyloid-beta, which forms plaques in the brain, is a cause of Alzheimer’s disease. A growing body of evidence suggests that the brain’s blood flow may also be affected by this phenomenon.

Researchers from the University of Manchester and the British Heart Foundation (BHF) have now discovered changes in the brain’s blood arteries as a result of stress. According to the study findings, new medications could be developed to assist battle the condition. Amyloid- 1-40 (A1-40), a smaller variant of the protein, builds up in the walls of the small arteries and reduces blood flow to the brain, according to the study.

The brain is starved when its arteries become narrower.
The constriction of the small arteries that cover the surface of the brain, known as pial arteries, is a key cause of memory loss in persons with Alzheimer’s disease. The brain’s blood and oxygen flow is regulated by these arteries, and if they get narrowed over an extended period of time, memory loss results.

A1-40 production in the pial arteries of Alzheimer’s-affected mice was discovered to be overly high, and the arteries of these animals were shown to be narrower than those of healthy mice. When A 1-40 enters cells that line blood vessels, it inhibits the activity of the BK protein, which typically signals to widen of blood vessels.

Alzheimer's disease - Wikipedia

Having a better understanding of how Alzheimer’s disease affects blood arteries could be an important breakthrough.
A cure for Alzheimer’s disease is proving to be a challenge for biomedical scientists. The authors of the current study believe their technique is unique, and that could be the difference between success and failure.

“Alzheimer’s disease has been the subject of more than 500 drug trials to date. According to Dr. Adam Greenstein, a BHF-funded researcher and Clinical Senior Lecturer in Cardiovascular Sciences at the University of Manchester, “all of them have targeted brain nerves and none of them have been successful.” Researchers have opened up new areas of inquiry to identify an effective treatment for Alzheimer’s disease by demonstrating how the disease impacts the small blood arteries, he explains.

In order to develop medications that can halt this process, the scientists must first determine which component of A 1-40 in particular blocks the BK protein. Research into Alzheimer’s disease has taken a significant step forward in the development of new therapeutic options.

A report on the study’s findings appeared in the prestigious scientific publication Proceedings of the National Academy of Sciences.

Alzheimer’s disease patients’ brain microcirculation is increasingly seen as a possible target for disease-modifying medications, reflecting a growing recognition of data showing cerebral blood flow is reduced in these individuals. In brain resistance arteries, however, there are still unknown pathogenic processes that underlie the blood flow problems. The APP23 mouse model of Alzheimer’s disease, in which the amyloid precursor protein is increased sevenfold, was used to investigate the roles of major vasodilatory pathways in cerebral arteries.

This model has neuritic plaques and cerebrovascular amyloid- accumulation similar to those found in Alzheimer’s patients. Pressure-induced (myogenic) constriction was enhanced in APP23 mice (18 months old) because of a profound reduction in ryanodine receptor-mediated, local calcium-release events (“Ca2+ sparks”) in arterial smooth muscle cells and a decrease in the activity of large-conductance Ca2+-activated K+ (BK) channels. Endothelial cell inward rectifier K+ (Kir2.1) channel dilatation was similarly hampered by this treatment. BK dysfunction was partially replicated in wild-type animals after an injection of Amyloid- 1- 40 protein into cerebral arteries, but there was no influence on Kir2.1 function.

Decreased blood flow and impaired functional hyperemia in Alzheimer’s disease patients could be attributed to a combination of K+ channel-mediated vasodilation abnormalities. Researchers should use these findings to devise new ways that can restore healthy cerebral blood flow and hence improve clinical outcomes.

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