Discovery could lead to development of drugs that halt disease progression and stop memory loss
Blood vessel breakthrough major step towards Alzheimer鈥檚 treatment
A breakthrough in our understanding of Alzheimer鈥檚 disease has revealed changes to blood vessels in the brain, potentially presenting a path for developing new drugs to help fight the disease, according to University of Manchester research funded by the British Heart Foundation (BHF) and published today in Proceedings of the National Academy of Sciences (PNAS)1.
Alzheimer鈥檚 Disease is traditionally thought of as a disease of the brain cells, where a protein called Amyloid-beta (A尾) accumulates and forms plaques. There is growing evidence that the blood supply to the brain is also affected, however, how this happens is unknown.
Now, researchers at the University of Manchester have found that a smaller version of the protein - called Amyloid-尾 1-40 (A尾 1-40) - builds up in the walls of the small arteries and reduces blood flow to the brain.
The surface of the brain is covered with small arteries, called pial arteries, that control the brain鈥檚 supply of blood and oxygen. If these arteries become narrowed for too long, the brain can鈥檛 get enough nutrients. This is one of the causes of memory loss seen in people with the disease.
When the team looked at pial arteries of older mice with Alzheimer鈥檚 that produced too much A尾1-40, they found that the arteries were narrower compared to those of healthy mice.
To date, over 500 drugs have been trialled as a cure for Alzheimer鈥檚 disease. All of them have targeted the nerves in the brain and none of them have been successful. By showing exactly how Alzheimer鈥檚 disease affects the small blood vessels, we have opened the door to new avenues of research to find an effective treatment
This narrowing was found to be caused by A尾 1-40 switching off a protein called BK in cells lining blood vessels. When it is working normally, BK sends a signal which causes arteries to widen.
To confirm that A尾 1-40 stopped BK from working properly, they soaked healthy pial arteries in A尾 1-40 and measured the signals sent by the BK protein after one hour. A尾 1-40 weakened these signals, which caused the arteries to narrow.
The researchers now plan to investigate which part of A尾 1-40 blocks the BK protein, so drugs to stop this from happening can be developed and tested as a much-needed treatment to prevent Alzheimer鈥檚 disease from progressing and save people the heartache of losing their memory.
Dr Adam Greenstein, lead BHF-funded researcher and Clinical Senior Lecturer in Cardiovascular Sciences at the University of Manchester said: 鈥淭o date, over 500 drugs have been trialled as a cure for Alzheimer鈥檚 disease. All of them have targeted the nerves in the brain and none of them have been successful. By showing exactly how Alzheimer鈥檚 disease affects the small blood vessels, we have opened the door to new avenues of research to find an effective treatment.鈥�
Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation said: 鈥淭his research is an important step forward in our understanding of Alzheimer鈥檚 disease. More than half a million people in the UK are living with the condition, and that number is set to rise as our population gets older. These findings could lead to a desperately needed treatment for this devastating condition.鈥�