From 'Criminal Minds' to chemistry: One ASU grad student’s journey to studying Alzheimer’s

Idara Akpan used to watch "Criminal Minds" with her mom. Now, she is putting her investigative curiosities to work as she develops new ways to detect and treat Alzheimer’s disease.

“I was always fascinated by how cases were solved by the tiniest bit of evidence, such as a trace chemical,” says Akpan, a graduate student at Arizona State University's School of Molecular Sciences in Professor Alexandra Ros’ research group. That fascination grew into a passion when she took her first chemistry class in high school.

“What immediately grabbed my attention was chemistry's ability to explain the world at the most fundamental level.

Now, Akpan is using chemistry to study Alzheimer’s disease — which affects roughly 7.4 million people in the United States — with the goal of contributing knowledge that helps doctors develop better ways to detect and treat it.

Her research focuses on amyloid beta, a protein fragment that can form sticky clumps called plaques in the brain. While it is widely accepted that amyloid beta is connected to Alzheimer’s disease, scientists are still working to understand exactly what role it plays.

Akpan is working to shed light on that mystery by looking at soluble oligomers — small clusters of amyloid beta that can move through brain fluid — because they may be more important to understand than the larger, more settled plaques. Their shape and structure can affect how they behave in the brain, but because they are constantly changing, they are difficult to capture and analyze.

She uses tiny, custom-built microfluidic devices — small lab platforms with channels and valves that can move and prepare minute amounts of fluid — to overcome that challenge.

These devices allow her to carefully isolate amyloid beta pieces with minimal sample loss, which is important when she is working with limited brain tissue samples.

When Akpan started studying at ASU, she was nervous about finding a place she could thrive. Then she found the Ros Lab.

Alexandra Ros, professor with the School of Molecular Sciences and the Biodesign Center for Applied Structural Discovery, has not only encouraged Akpan to become a better analytical scientist but also to gain new skills, including learning microfabrication, which was key in designing and manufacturing the microfluidic devices.

“The biggest factor she has helped me with is to analyze the problem,” says Akpan about Ros. “Through her mentorship, I have learned that research is more than just conducting experiments.”

“I have been mentoring Idara for approximately three years and have watched her grow substantially both as a PhD student and a scientist. What stands out most is the enthusiasm and dedication she brings to her work. She has taken ownership of a challenging project and approaches it with the independence of an established researcher with strong critical-thinking skills,” says Ros.

Akpan uses a double-layered polydimethylsiloxane (PDMS) microfluidic platform paired with MALDI mass spectrometry, termed MIMAS. MIMAS can handle many of the precise preparation steps needed for her to conduct mass spectrometric analysis on the proteins.

Mass spectrometry is important to Akpan’s research because it helps her identify which forms of amyloid beta are present. MALDI is particularly helpful because it is relatively gentle, meaning that the amyloid beta clusters may stay together long enough to be detected. Harsher analysis methods could break apart some of these delicate clusters before they can be studied.

MALDI can also get more detailed with tandem mass spectrometry (MS/MS), which intentionally breaks the selected molecule into smaller pieces to be studied — like taking apart a Lego model to see how it was built.

For MALDI mass spectrometry, Akpan relies on the Core Research Facilities’ Mass Spectrometry Core, where she has gained hands-on expertise with the Bruker rapifleX, a high-performance MALDI mass spectrometer housed in the facility. Guided by Core Facilities staff and Bruker engineers, she became proficient in using the instrument to conduct her research.

“Idara is the most experienced member of my lab in mass spectrometry and has become an important resource for others working in this area,” says Ros. “She has helped mentor fellow students and has been instrumental in getting several mass spectrometry-based projects started, sharing both her technical expertise and practical knowledge.”

One thing Akpan is excited about with the future of the work goes beyond studying amyloid beta oligomers. It’s about improving the way the microfluidic devices are fabricated. This would allow her and other researchers to study the proteins directly on the brain tissue samples instead of having to first move them into the device.

That improved device functionality aligns with another of Akpan’s future goals. It would help her map where different forms of amyloid beta appear in an Alzheimer’s patient’s brain and help researchers better understand how the disease develops in different areas of brain tissue. Over time, that kind of understanding could help scientists move toward earlier diagnoses and more effective treatments.

While Akpan’s project focuses on a protein involved in Alzheimer’s, she feels it can be tailored for other protein targets. The versatility of the microfluidic devices would open doors for researchers looking at proteins involved in other diseases — like Parkinson’s, Lewy body dementia, ALS and Huntington’s — that are not well understood and need more effective treatment options.

“Something that started as a love for TV shows has turned into a lifelong career. This motivates me to continue exploring these hard problems and hopefully get a better understanding of conditions impacting millions of people,” says Akpan.