As per University of Manchester studies funded by the British Heart Foundation (BHF) and published in Proceedings of the National Academy of Sciences, a significant development in the understanding of Alzheimer’s disease has put forth changes to blood vessels in the brain, ideally presenting a way for developing new drugs that help fight the disease.
Alzheimer’s is typically considered to be a brain disorder in which a protein called Amyloid-beta accumulates and forms plaques in the brain cells. There is mounting evidence that the brain’s blood supply is also harmed; however, how this occurs is uncertain. Researchers at the University of Manchester have discovered that a smaller version of the protein known as Amyloid-β 1-40 accumulates in the walls of tiny arteries and restricts blood flow to the brain.
The cortex of the brain is covered with tiny arteries known as pial arteries, which regulate the flow of blood and oxygen to the brain. The brain cannot acquire adequate nourishment if these arteries are restricted over an extended period of time. This is one of the reasons for memory loss in Alzheimer’s patients.
When the researchers examined the pial arteries of older mice with Alzheimer’s disease that produced too much A1-40, they discovered that they were narrower than those of healthy mice.
The narrowing was discovered to be triggered by A1-40 turning off a specific protein BK in blood vessel cells. When BK is in good working order, it sends out a signal that induces arteries to expand. Researchers immersed healthy pial arteries in A 1-40 and examined the impulses sent by the BK protein after an hour to confirm that A 1-40 blocked BK from working properly. These signals were weakened by A1-40, causing the arteries to constrict.
The researchers will now examine which components of A1-40 inhibit the BK protein so that medications to prevent this can be produced and evaluated as a much-needed therapy to halt the progression of Alzheimer’s disease and spare individuals the agony of losing their memories. To date, approximately 500 medications have been trialled as a cure for Alzheimer’s disease, said the lead BHF-funded researcher and Clinical Senior Lecturer in Cardiovascular Sciences at the University of Manchester, Dr Adam Greenstein. All have tried to target the nerves in the brain, but none of them have succeeded. They have opened up new areas of inquiry to identify an effective cure for Alzheimer’s disease by revealing how the disease affects small blood vessels.
This research is a major step forward in the understanding of Alzheimer’s disease, said Associate Medical Director of the British Heart Foundation, Professor Metin Avkiran. Well over half a million individuals in the UK suffer from the disease, and the figure is expected to climb as the population ages. These discoveries could contribute to a much-needed cure for this life-threatening disease.
