Dr Shefeeq Theparambil gives an insight into the research being carried out through two PhD projects here at Lancaster University.

Our brain needs a large amount of energy to function properly, and this energy mainly comes from glucose. However, the brain stores very little glucose, so it depends on a continuous supply of glucose and oxygen through blood flow. To meet this constant demand, the brain is densely filled with tiny blood vessels called arterioles and capillaries. These vessels can widen (dilate) whenever neurons become active and require more energy.

This ability of blood vessels to respond to neuronal activity is crucial for brain health. Unfortunately, it declines with ageing, dementia, and other neurodegenerative diseases, leading to reduced nutrient delivery and poor clearance of toxic waste. In Alzheimer’s disease and some forms of dementia, the brain’s blood vessels lose this adaptive capacity even before clinical symptoms appear. This has led many neuroscientists to propose that reduced blood flow may not only worsen disease progression but could also contribute to its onset, adding a new dimension to our understanding of Alzheimer’s pathology.

A key mystery is how neurons communicate their “energy needs” to blood vessels. The ARUK PhD project, led by Adam Johnson, will explore the role of astrocytes in this communication. Astrocytes are star-shaped glial cells that line up along blood vessels and make close connections with neurons. Because of this unique position, they can “listen” to neuronal signals and translate them into messages that control blood vessel dilation. In this way, astrocytes act as a bridge between neurons and blood vessels, helping to deliver energy and clear harmful molecules such as amyloid-beta from the brain.

A second PhD project, funded by Defying Dementia and the Faculty of Health and Medicine and led by Ava Brand, will study how astrocytes take up glucose from blood vessels and how this process becomes impaired in Alzheimer’s disease. She will compare brain cells derived from healthy individuals and Alzheimer’s patients to find ways to boost astrocytes’ capacity to supply energy to neurons, potentially restoring healthy brain metabolism and function.

Together, these two projects complement each other by uncovering the mechanisms that boost blood flow and enhance glucose uptake in the brain. Understanding how astrocytes coordinate these processes may reveal new ways to restore energy balance and improve brain function in Alzheimer’s disease.

Understanding the mechanisms that regulate energy supply and metabolism in the brain could have huge benefits. It may help identify drug targets that can boost blood flow and metabolism, protecting neurons and potentially rescuing cognitive function in Alzheimer’s disease and other neurodegenerative disorders. Reduced brain blood flow and metabolism is often prominent early in disease, sometimes even before any clinical symptoms appear, so these insights could support early intervention and prevention strategies.