Print This PostHello, my name is Rahul Sidhu, and I am a third-year PhD student at the University of Sheffield, working in the Sheffield Neurovascular Lab. I thought I would share a little insight into what my research is all about. Alzheimer’s disease is the leading cause of dementia, yet its complexity means we still do not fully understand it.
This is where our lab and my research come into play. Our research is classified as basic science, but there is nothing “basic” about it. My research focuses on the connection between heart disease and Alzheimer’s disease; specifically, how problems with blood flow might speed up cognitive decline.
In this blog, I will take you through why the brain relies on a constant blood supply, what neurovascular coupling is, how conditions like atherosclerosis (a type of heart disease) can disrupt this, and why this could be making Alzheimer’s disease worse. My work uses preclinical models to explore this link, with the hope of finding new ways to slow or even prevent dementia.
When people think about Alzheimer’s disease, they usually picture memory loss and confusion. What they do not often think about is the brain’s need for energy and just how critical the cardiovascular system is in keeping it fueled. That is where my research makes a difference. If we can figure out how heart health impacts brain health, we might be able to find new ways to slow down dementia.
The brain is an energy-hungry powerhouse. Despite only making up 2% of our body weight, the brain takes a massive 20% of our total blood supply. This is because neurons – the cells that make up the brain – are incredibly energy demanding. They need a constant supply of oxygen and glucose to function and keep the brain cells healthy. However, the brain does not have any back up energy reserve. Fortunately, the brain has a remarkable way of getting its energy. Our brain is a truly miraculous organ, they are highly vascularised, with approximately four hundred miles of blood vessels. This is the distance from London to Edinburgh. We use these blood vessels to get the fuel our brains need, through a process called neurovascular coupling.
This is a mechanism where active neurons signal to nearby blood vessels, telling them to widen and increase blood flow. This ensures that areas of the brain which are working hard (for example when you are solving a tricky problem, recalling a memory, moving or walking, or you see something interesting) get the energy they need to function. But what happens if this finely tuned system starts to fail? That is where things get interesting.
Neurovascular Dysfunction: When the Blood Supply Falters
If neurovascular coupling breaks down, neurons do not get enough fuel and energy. Over time, this can lead to cognitive problems and even increase the risk of neurodegenerative diseases like Alzheimer’s.
Think of it like a car running low on fuel. At first, it might sputter and slow down, but if the tank stays empty for too long, the engine will eventually stop working.
The same happens to brain cells. They might cope for a while, but without a steady supply of oxygen and glucose, they weaken and die.
Fun Fact: Your brain has about 400 miles of blood vessels—roughly the distance from London to Edinburgh! These tiny highways deliver oxygen and nutrients, but if they get clogged or damaged (like in heart disease), it can speed up cognitive decline and increase the risk of Alzheimer’s. So, keeping your heart healthy is also a great way to protect your brain! 🧠❤️
Alzheimer’s disease also has many risk factors which can further the progression of the disease or increase the likelihood of developing the disease in the first place, such as type 2 diabetes, high blood pressure, and cardiovascular disease. One major risk factor condition that can interfere with blood supply to the brain is heart disease—particularly atherosclerosis. Atherosclerosis is a heart disease where fatty deposits known as plaques build up inside arteries, narrowing them and making them less flexible. This restricts blood flow, meaning that the organs supplied by those arteries—including the brain—receive less oxygen and nutrients. This can have profound consequences for brain health. If blood flow to the brain is reduced, neurovascular coupling is impaired, and neurons struggle to function properly. Over time, this could accelerate cognitive decline and make conditions like Alzheimer’s worse. Interestingly, many of the risk factors for heart disease, such as high blood pressure, diabetes, obesity, and smoking, are also risk factors for Alzheimer’s disease. So, could heart disease be speeding up the progression of Alzheimer’s? That is exactly what I’m trying to find out.
Understanding Alzheimer’s Disease: The Role of Tau
Inside the brain, Alzheimer’s is linked to two key proteins: amyloid-beta and tau. – Amyloid-beta forms sticky plaques between neurons, disrupting their communication. – Tau, on the other hand, normally helps neurons maintain their internal transport system, which carries nutrients and signals from one part of the cell to another. In Alzheimer’s, tau proteins become abnormal, detach from the transport system and clump together, forming neurofibrillary tangles. This disrupts the neuron’s function, eventually leading to cell death.
My Research: How Heart Disease and Alzheimer’s Interact
At the Sheffield Neurovascular Lab, my research uses preclinical models of human disease to study tau’s role in Alzheimer’s and how it interacts with vascular problems like atherosclerosis. If tau pathology worsens when blood flow is impaired, it could mean that heart disease exacerbates Alzheimer’s progression.
The different models include a model of Alzheimer’s where there is a build-up of tau in the brain, a model of heart disease where fatty deposits build up, and a mixed model of both diseases. This model combines both conditions, letting me explore whether heart disease makes Alzheimer’s worse and how. To gain a comprehensive understanding of neurovascular coupling, we use various advanced imaging techniques that provide a glimpse into brain activity. One of our approaches involves optical imaging, where we shine wavelengths of light onto the brain. This enables us to track changes in blood oxygenation, helping us explore how Alzheimer’s disease and heart disease may affect blood volume in the brain. Additionally, we employ methods that simultaneously measure neural brain activity and blood oxygenation levels.
By capturing both aspects at the same time, we can gain deeper insights into the underlying mechanisms at play.
Why does this research matter right now? Most treatments for Alzheimer’s focus on monoclonal antibodies to remove these toxic proteins. However, what if we could tackle Alzheimer’s from a different angle, by improving vascular health. If my research confirms that heart disease accelerates Alzheimer’s, it could open the door to new treatments. Instead of just targeting plaques and tangles, we might be able to protect the brain by improving blood flow. This could mean: 1. New drugs that boost neurovascular function. 2. Lifestyle changes (like exercise and diet) that support vascular health. 3. Early screening for heart disease to reduce dementia risk later in life. It is an exciting prospect and one that could change the way we fight dementia.
One of the most exciting things about this field is its potential to make a real difference. If we can prove that vascular health affects Alzheimer’s progression, then improving cardiovascular function might become a new strategy for preventing dementia. It’s a simple idea with huge potential: protect the heart, protect the brain. In the future, this could mean: New treatments aimed at restoring neurovascular coupling; Personalized medicine, where people at risk of both conditions get targeted therapies.
In summary, my PhD research is all about exploring how heart disease influences Alzheimer’s progression. By studying vascular dysfunction, tau pathology, and cognitive decline, I hope to uncover new ways to slow or prevent dementia. Our bodies work as integrated systems, what is good for the heart is good for the brain.
Rahul Sidhu
Author
Rahul Sidhu is a PhD student at The University of Sheffield, focusing on the effects of heart disease on dementia in preclinical models of Alzheimer’s disease. His research aims to uncover how cardiovascular health influences neurodegenerative conditions, potentially leading to novel therapeutic strategies.
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