Pharmacy graduate students searching for early markers of Alzheimer’s disease

For many suffering from Alzheimer’s disease, alterations in the brain can begin 10 or more years before the appearance of symptoms and a diagnosis. Early detection in Alzheimer’s is critical and the search for those early markers drives the research of Harrison School of Pharmacy graduate student Sharay Setti.

Setti, a fourth-year doctoral student working under Associate Professor Miranda Reed in the Department of Drug Discovery and Development, was recently recognized for her work with a $10,000 fellowship from the American Foundation for Pharmaceutical Education. It marks the third consecutive year for Setti to receive the fellowship, which provides recognition and support for a diverse group of students as they pursue advanced pharmaceutical sciences education. Additionally, she was recently selected for one of the inaugural Auburn University Center for Neuroscience Initiative fellowships.

“Sharay is a hard-working student that is driven and passionate about research,” said Reed. “Her critical thinking skills and ability to problem solve have been critical for this project given how little existing work has been done in this area.”

Setti’s research interests and the ultimate goal of her dissertation involve early detection of Alzheimer’s disease. The goal of her project is to understand how Alzheimer’s disease spreads from one of the earliest brain regions affected in the disease progression, the lateral entorhinal cortex, or LEC, to other regions in the brain. Her work will also aid in the creation of a memory task sensitive to alterations in the LEC that may one day lead to a better diagnostic for early detection of Alzheimer’s.

“I think Alzheimer’s is such a tragedy for the patients and their caretakers and I would really like to see research reach a state where we have really sensitive markers of disease that can be detected early on,” said Setti. “It isn’t likely to be feasible to screen everyone for these biomarkers, therefore, I want to aid in the development of early diagnostic tasks so that physicians can administer them as a screening tool. Then, if patients perform poorly on these tasks, they can be recommended for further testing.”

Setti earned her bachelor’s and master’s degrees from the University of North Carolina at Wilmington. She then made her way to Auburn to pursue her doctorate and work in Reed’s lab. She is on pace to complete her degree this December.

“I knew that I was interested in working in the field of Alzheimer’s disease and aging since I was an undergrad,” said Setti. “I had heard of Dr. Reed and her research through a professor that went to graduate school with her, and I really admired her as a researcher.”

Since joining Reed’s team, Setti has focused on understanding Alzheimer’s disease, specifically focusing on early changes in the LEC, a sub-region of the entorhinal cortex that is part of the hippocampal formation. The LEC projects to the hippocampus, a brain region that is very important for learning and memory. Alterations that begin in the LEC ultimately spread to the hippocampus and it is believed that this spread is mediated by neuronal activity alterations.

By developing memory tests with something as simple as an iPad, Setti hopes to identify early markers and memory deficits that are associated with Alzheimer’s. The LEC is believed to play an important role in a form of memory called associative memory, which is the ability to learn and remember the relationship between unrelated items.

“Using an iPad, you might show a patient a series of objects paired with different backgrounds, or contexts, and after some delay, patients are shown object and background combinations, some of which were shown previously and some of which are similar but new,” said Setti. “They are asked to assess whether they recall having ever seen a particular item paired with a particular context and background. Generally, we would expect patients at risk for Alzheimer’s to make more false positive errors, in which they believe they have seen an object in a particular context even when they have not seen that exact combination.”

Existing diagnostics focus on regions of the brain affected later on in the disease. The problem that arises is by the time those regions are affected, the damage has been done. Setti believes the LEC is the key and identifying changes there can provide opportunities to stop the disease before it spreads.

“The LEC is the first region affected by tau pathology in Alzheimer’s disease. Certain brain regions falter early in neurodegenerative disorders, and the LEC has been identified as the site where some of the first abnormalities appear in Alzheimer’s,” said Reed. “However, the role of the LEC in memory is poorly understood, and our current diagnostic memory tasks assess alterations in brain regions affected much later in the disease process. Thus, understanding the role of LEC in memory may lead to the development of novel memory diagnostics that assess LEC functioning, thereby allowing for earlier diagnosis of Alzheimer’s.”

With graduation on the horizon, Setti hopes to continue working in neurodegenerative disorders, specifically as it relates to learning and memory. She is also interested in pursuing research on the interaction between traumatic brain injury and the development of Alzheimer’s.