Longevity Briefs: How Is Blood Supply Reduced In Alzheimer’s Disease?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Alzheimer’s is typically thought of as a disease that affects brain cells, and is thought to be driven at least in part by the aggregation of the protein Amyloid-beta (Aβ) into amyloid plaques, which damage neurons. There’s also evidence that blood flow to the brain is reduced, but how this occurs isn’t yet fully understood. Tiny arteries called pial arteries cover the surface of the brain and control its supply of blood. These arteries can become narrowed over time in Alzheimer’s, meaning that regions of the brain don’t receive enough nutrients. This is thought to be one of the causes of memory loss in people with the disease.

What did the researchers do: In this study, researchers looked at mice engineered to produce Amyloid-β 1-40, a smaller subtype of Amyloid-β. These mice develop Alzheimer’s disease in old age. The researchers compared the pial arteries in these mice to those of healthy mice, and found that the arteries of the Amyloid-β 1-40 mice were narrower.

Previous research had shown that injections of Amyloid-β could block a protein in the membranes of neurons called BK. BK is a channel protein that can open and close to allow the passage of potassium ions, which acts as an electrical signal. This channel is also present in blood vessels and causes them to widen when activated. The researchers wanted to see whether Amyloid-β 1-40 also affected BK in pial arteries, and whether this might explain their progressive narrowing.

Key takeaway(s) from this research:

• BK activity was reduced in the pial arteries of mice overproducing Amyloid-β 1-40
• Pial arteries isolated from healthy mice narrowed after an hour of soaking in Amyloid-β 1-40, and activity of BK was reduced.

This potentially opens the doors for Alzheimer’s treatments that target the interaction between Amyloid-β 1-40 and BK. For this, researchers will first need to figure out exactly how this interaction works, such as which part of the Amyloid-β 1-40 protein is responsible for blocking the BK channel.

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. 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.

-Dr Adam Greenstein, lead BHF-funded researcher and Clinical Senior Lecturer in Cardiovascular Sciences at the University of Manchester