Blood flow in the brain is often compromised in people with Alzheimer’s dementia, and is thought to contribute to the functional and cognitive decline associated with the disease. Laboratory research published in the PNAS journal (Proceedings of the National Academy of Sciences) has provided new clues about the biological causes of brain blood vessel dysfunction in Alzheimer’s disease (AD), identifying pathways that could potentially be targeted for future drug development. The brain microcirculation consists of tiny blood vessels and arteries, which help perfuse the brain with blood. In people with AD, the brain microcirculation can be compromised, with reduced blood flow, and dysfunctional responses to stimuli. This dysfunction is at least partly driven by the presence of amyloid proteins in and around blood vessels, which is thought to lead to some of the functional and cognitive changes that people with AD experience during disease progression. In their PNAS article, a team of researchers led by Prof. Adam Greenstein of Manchester University (UK) used an animal model of AD to understand how blood vessels of the brain microcirculation are altered in AD. By exposing pial arteries from AD mice to different stimuli, they were able to observe that the contraction of these arteries was significantly altered compared to mice without AD.
The arteries from AD mice contracted and narrowed much more extensively, and were less able to dilate than arteries from mice without AD. In particular, exposure of arteries to amyloid proteins, the primary component of the prevalent amyloid plaques in the brains of people with AD, caused the arteries to narrow substantially. By using molecular tools, the researchers were able to identify a specific ion channel that was dysfunctional in arteries from AD mice, which may explain why they were more prone to contract and, therefore, restrict blood flow to the brain. Further studies are now required to understand the importance of these findings in the clinical context. To read the article: https://www.doi.org/10.1073/pnas.2204581119
