Researchers win $20.5 million NIH grant to beat Alzheimer’s disease and related dementias

A team of researchers from the Sanders-Brown Center on Aging (SBCoA) at the University of Kentucky has received a $20.5 million grant from the National Institute on Aging (NIA) of the National Institutes of Health (NIH).

The P01 award exemplifies team science, helping to support approximately 35 researchers in six different labs who will work on four main projects, all with a common theme.

We’re a highly collaborative team at Sanders-Brown, so we work together all the time anyway. A project like this is natural for us. We are a group of researchers who are all trying to beat Alzheimer’s disease and related dementias.”

P01 Leader Chris Norris, Ph.D., Professor in the Department of Pharmacology and Nutritional Sciences at the UK College of Medicine, and Associate Director at SBCoA

The big project is called Strategies for Targeting Astrocyte Reactivity in Alzheimer’s Disease and Related Dementias (STAR-ADRD). Norris says the acronym they came up with has a double meaning as astrocytes -; the purpose of their project -; are star-shaped cells.

Alzheimer’s disease and other forms of dementia are diseases caused by various pathologies. With this grant, the research team plans to study the role of astrocytes in these disorders.

“Astrocytes are, in some ways, a forgotten cell in neurodegenerative diseases,” Norris said. “For many years they were thought of as support cells for things like neurons. Neurons communicate a lot with each other to form memories that neuroscientists study. Neurons eventually die as the disease progresses. Alzheimer’s and related dementias.

Norris says astrocytes have many branches that wrap around blood vessels in the brain. These branches also wrap around many connections between neurons. Because of this arrangement, astrocytes are well positioned to help deliver energy, nutrients, and blood oxygen to neurons.

“The reason we are so interested in astrocytes is that they show very obvious changes with neurodegenerative diseases like Alzheimer’s disease, where blood flow and communication between neurons are disrupted.”

When Alzheimer’s disease was first described, Norris says the pathology shown included reactive astrocytes. He says these cells tended to cluster around areas where there was pathology, such as amyloid deposits in the brain -; characteristic of Alzheimer’s disease.

“So we’ve known about reactive astrocytes for over a century, but we don’t really know what these cells do,” Norris said. “Most of the time when people study reactive astrocytes, they mark them in post-mortem tissue, especially around plaques, or around sclerotic blood vessels, or things like that. But we really don’t know what what these cells are doing there. Are they reacting to this damage? Are they causing this damage? We need to study them for function or dysfunction and that is one of the main goals of our new grant .

The four distinct projects that make up the global enterprise are led by world leaders in their respective fields. Donna Wilcock, Ph.D., will lead her lab in studying the connections of astrocytes that circulate around blood vessels; Pete Nelson, MD, Ph.D., leads a project studying a potassium channel that acts as a metabolic sensor in astrocytes; and Olivier Thibault, Ph.D., and his lab will examine how astrocytic insulin receptors help control calcium metabolism, blood flow, and homeostasis. Norris leads a project on astrocytes and the uptake of glutamate, an excitatory neurotransmitter. Pradoldej Sompol, Ph.D., Yang Jiang, Ph.D., and Yuriko Katsumata, Ph.D., each lead critical service nodes that support the four research projects.

“The NIH and NIA place great importance on addressing Alzheimer’s disease and related dementias,” Norris said. Congress has allocated a lot of money to fight the disease, so people are really interested right now. It’s kind of the health care crisis of our generation.”

There is currently no cure for Alzheimer’s disease, and Norris says FDA-approved treatment options are lacking.

“Current treatments aren’t exactly good at reversing dementia or preventing it. They have rather mild effects on individuals, so there’s a lot of room to look for other potential drug targets,” Norris said.

Norris says astrocytes are an attractive cell to study for this therapeutic potential, because their actual function and contribution to pathology has been taken for granted for decades.

“If we can understand what reactive astrocytes are doing in terms of pathology, then we may be able to develop treatments to target those pathways and hopefully alleviate pathology,” he said.

SBCoA is ideally located for a project like this. The center is recognized worldwide for its brain bank as well as its team of researchers and volunteer researchers.

“They went above and beyond to participate in our studies and donate brain tissue and other nervous system tissue to help us understand what causes dementia,” Norris said. “All the studies that we do in animal models, we have parallel studies in human brain or in human tissue samples from our brain and our biofluid bank. So we can look at Alzheimer’s pathology and cerebrovascular pathology and then study how astrocyte signaling differs across these different disease states.Then we can go into animal models and target these astrocyte pathways to see if brain function is improved or not.

Norris says the purpose of P01 grants is to fund large, multi-laboratory projects built around a theme. The total product is then assumed to be greater than the sum of its parts. With teamwork and collaboration already at the forefront for each of the researchers involved, this is a project they are all excited to be part of and very optimistic about its future.

“This grant is very timely. It really comes at the right time. We are all in a great position to target astrocytes and understand what they do in brain pathology and dementia. Everyone on this team is just amazing” , Norris said.

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