Alzheimer's and Dementia

How Does Disrupted Blood Flow in the Brain Lead to Dementia? Scientists Explain

Impaired blood flow to the brain has long been considered a key factor in the development of many types of dementia, most notably Alzheimer's disease. Now, researchers have made a new scientific discovery that may shed light on the precise mechanism by which this flow is disrupted, opening the door to promising treatment avenues.

A research team from the University of Vermont in the United States has revealed the role of a single fatty molecule in maintaining the delicate balance of blood flow within the brain. The study, conducted on mice with Alzheimer's disease, showed that disruption of this molecule leads to widespread cerebral circulatory problems, a disruption that could be partially rectified when the balance was restored to its normal level.

"This discovery represents a major step forward in our efforts to understand dementia and neurovascular diseases, and perhaps even prevent them," says pharmacologist Osama Harraz, one of the study's lead researchers.

The researchers based their study on an analysis of the role of endothelial cells, the cells that line the inner walls of blood vessels. Attention was focused on a protein known as Piezo1, a mechanosensor that responds to pressure within blood vessels and plays a role in regulating blood flow.

The results showed that overactivation of this protein leads to disrupted blood distribution within the brain. This is where the lipid molecule PIP2 comes in, acting as a "natural brake" on Piezo1 activity and maintaining the necessary balance.

How does the imbalance occur in Alzheimer's?

Normally, PIP2 levels are low in active brain regions, allowing Piezo1 to be activated and increasing blood flow to areas that need more oxygen and energy. However, in mouse models of Alzheimer's disease, the researchers observed that levels of this molecule are abnormally low.

This chronic decrease leads to Piezo1 overactivity, causing blood flow to be directed to areas that don't actually need it, thus disrupting overall cerebral circulation. Most importantly, restoring PIP2 levels to normal helped restore patterns closer to healthy blood flow.

Although the study was conducted only in mice and over a short period, its findings are particularly significant for vascular dementia, one of the most common forms of dementia, where impaired blood flow is a key factor in its development. Evidence also suggests that vascular disorders play a complementary role in Alzheimer's disease, alongside the accumulation of toxic proteins in the brain.

Since blood flow controls the delivery of oxygen and nutrients to nerve cells, maintaining this balance is essential for normal brain function, not just for preventing dementia.

Alzheimer's and Dementia

Future Prospects

The researchers believe that understanding the precise interaction between PIP2 and the Piezo1 protein will be the next crucial step in developing therapeutic strategies that target improving cerebral blood flow and potentially slowing cognitive decline. Harraz concludes, "We are now beginning to decipher the complex mechanisms behind these devastating diseases, and with this understanding, we can seriously consider turning biological knowledge into future treatments."