Researchers at the University of Manchester have discovered changes to blood vessels in the brain in people with Alzheimer’s, potentially opening up a path for the development of new drugs to fight the disease.
The research was funded by the British Heart Foundation and results have been published in “Proceedings of the National Academy of Sciences”.
Alzheimer’s is traditionally considered a disease of brain cells, where a protein called Amyloid-beta accumulates and forms plaques. The research has discovered a smaller version of that protein – named Amyloid-β 1-40 (Aβ 1-40) – builds up in the walls of small arteries, reducing blood flow to the brain. If the arteries are narrowed for too long, the brain cannot get enough nutrients, leading to memory loss.
The team examined the pial arteries of older mice with Alzheimer’s that produced too much Aβ1-40 and found that the arteries were narrower compared to those of healthy mice. They discovered that the narrowing was caused by Aβ 1-40 switching off BK protein, which sends a signal causing arteries to widen.
They confirmed their findings by soaking healthy pial arteries in Aβ 1-40 to measure the signals sent by the BK protein after an hour. Results showed that Aβ 1-40 weakened these signals, leading to the narrowing of the arteries.
The researchers plan to investigate further, so that drugs can be developed to stop this from happening, providing a much-needed treatment to prevent Alzheimer’s from progressing.
“To date, over 500 drugs have been trialled as a cure for Alzheimer’s disease. All of them have targeted the nerves in the brain and none of them have been successful,” said Dr Adam Greenstein, lead researcher and Clinical Senior Lecturer in Cardiovascular Sciences at the University of Manchester. “By showing exactly how Alzheimer’s disease affects the small blood vessels, we have opened the door to new avenues of research to find an effective treatment.”