Interest in Neuroscience Leads UVA Researcher to Alzheimer’s Insights That Could Improve Treatment

Today, El-Ghazawi knows that there is one thing that occurs years or even decades before symptoms of Alzheimer’s appear: damage to the blood vessels in the brain. 

In a paper in Communications Biology, a Nature portfolio journal, pre-published on June 8, El-Ghazawi found evidence that pericytes — a type of brain cells that support capillaries, the smallest of the brain’s blood vessels — may play a larger role in Alzheimer’s disease than previously recognized. His research found that pericytes communicate differently with other cell types in the brain across brain regions. He also found differences in how pericytes communicate in men and women.

“Impairments to the blood vessels have been shown to be one of the earliest phenomena that occur in Alzheimer’s disease, appearing years to decades prior to clinical disease onset,” El-Ghazawi said. 

“Understanding why vessel impairments happen is really important for this disease because it could open new routes of intervention and diagnosis.”

Unlike neurons, or nerve cells, which have been studied extensively, pericytes remain relatively understudied and therefore less understood.

“Pericytes are really important in the brain — they ensure that the capillaries are doing what they need to do in response to what the brain needs. I wanted to focus on pericytes to understand their role in communicating with other cell types, and how that is changed in the context of Alzheimer’s disease.” 

Why Alzheimer’s is so Complex

Alzheimer’s affects various regions of the brain, and each is impacted differently as the disease progresses. In addition, Alzheimer’s disease impacts men and women in different ways. Women are at a much higher risk of developing the disease than men — about two-thirds of patients in the U.S. are female. 

That statistic holds even when researchers account for longer lifespans in women, El-Ghazawi said.

…We found that there were brain-region and sex-associated differences that were seen in how pericytes communicate with these other cell types.

It’s unclear why, and motivated by this uncertainty, El-Ghazawi’s goal was to understand whether pericytes are part of the reason to get closer to early detection and treatment. 

His team looked at computational data from various groups, comparing the difference in communication between pericytes and other cells. 

They contrasted how pericytes communicate with other cells in two distinct brain regions from the same donors. They also looked at cell communication between donors who were male and had Alzheimer’s, donors who were male and healthy, female donors who had Alzheimer’s and healthy female donors.

“Across that, we found that there were brain-region and sex-associated differences that were seen in how pericytes communicate with these other cell types,” El-Ghazawi said.

The data confirmed that sex and brain regions make a difference — and that personalized treatment based on these variations could lead to better results.

Shayn Peirce-Cottler, who chairs the biomedical engineering department and supported the research as a co-author and mentor to El-Ghazawi, said his findings help pave the way for improved treatment options. 

Publication in the journal, she added, “highlights the broad scientific impact of these findings and their potential to guide future precision therapies that target the brain’s vascular system.”

Pericytes Matter More Than You’d Think

The study is one of several publications that make up El-Ghazawi’s dissertation research, including a review of studies on the link between pericytes, Alzheimer’s and diabetes. 

“In both projects, I found that the role of pericytes is maybe more important than we might have once thought,” he said. “I also realized that if better therapies are your ultimate goal, you can’t just look at a particular cell type in isolation. 

“Now, what I really want to pursue more is the interaction between these cell types throughout the disease and what’s happening. Because I think looking at how these players work together will give us a much better understanding of these sorts of complex diseases.”

Co-author Yashasvisai Veeramasu, who graduated in May with a B.S. in biomedical engineering, has been involved in all three of El-Ghazawi’s projects and is staying at UVA as a post-baccalaureate researcher to continue some of the work.

“This research was especially meaningful to me because of my personal experience with my grandfather’s ongoing battle with Alzheimer’s,” she said. 

Changing Lives: Kindling the Spark

El-Ghazawi’s hospital experience after earning his bachelor’s was just the beginning of his interest in neurodegenerative disease research.  

“I wanted to help improve patient lives from a neurological standpoint,” he said. “So, when I came back to UVA, I wanted to work on neurodegenerative diseases.” 

Peirce-Cottler brought the necessary expertise on pericytes and connected him with his co-mentor, Ukpong Eyo, an associate professor of neuroscience and one of the study’s co-authors.

“They gave me the trust and support I needed,” El-Ghazawi said. 

Eyo described El-Ghazawi as “a great mind to grow and learn from” with “great respect for the scientific process and his mentors.”

El-Ghazawi’s relentless intellectual curiosity impressed both professors.

“That curiosity gave him the confidence to tackle problems that others had not addressed and to develop entirely new experimental and computational tools when existing approaches fell short,” Peirce-Cottler said.

The next step for El-Ghazawi is a postdoctoral position in assistant professor Alice Stanton’s lab at Massachusetts General Hospital and Harvard Medical School starting this fall. It’s a prestigious appointment with exciting opportunities to dig deeper into neurodegenerative diseases like Alzheimer’s. 

For now, though, he’s wrapping up his Ph.D. and enjoying the support system he’s built on Grounds.

“What I love about UVA is that everybody’s so approachable and just — human,” El-Ghazawi said. “There’s that support and help and excitement for one another. It’s a really nice place to be for a trainee.”