Chad Pollard (’22), cell biology PhD student and BYU’s 2022 Student Innovator of the Year, is on a mission to revolutionize Alzheimer’s disease diagnostics.
Alzheimer’s disease is arguably the most devastating form of dementia. It progressively impairs memory, cognition, and, in later stages of the disease, more basic aspects of daily living. Alzheimer’s is the most common form of dementia and the sixth leading cause of death in the United States. Currently, approximately 6.2 million Americans are diagnosed with Alzheimer’s, but it is a disease scientists still don’t fully understand.
This hole in academic knowledge has presented major challenges for diagnosing patients in the early stages of the disease, when pharmaceutical and lifestyle interventions are the most impactful to slowing the degeneration. This fact, combined with the projection that the number of individuals with Alzheimer’s disease could almost triple by 2060, means that effective diagnostic tools are critical.
An estimated 6.2 million people in the U.S. are currently living with Alzheimer's disease. This number is projected to nearly triple to 14 million by 2060.
The initial causes and main drivers of Alzheimer’s disease remain highly controversial, but it is universally accepted that the disease causes brain deterioration and neuron death. Currently, the primary way to diagnose Alzheimer’s disease is based on the development of clinical cognitive symptoms such as memory loss, difficulty completing familiar tasks, and changes in mood and personality, among others. By the time these symptoms appear, however, the disease is often in later stages of progression, when there is little that can be done to slow it.
“That’s why we have received all this attention,” Pollard says. “Since we started this project, we’ve learned that there are thirty FDA-approved drugs that are designed to prevent cell death and may be useful in Alzheimer’s disease. But none of them have been able to hit the market because they’re only useful if they’re administered before symptoms occur.”
Pollard has learned from his research is that there’s no concrete way to diagnose Alzheimer’s, or other neurodegenerative diseases like ALS or Parkinson’s disease, before symptoms occur. And “once symptoms set in, it’s too late.”
BYU’s Jenkins Lab was instrumental in Pollard’s education. Pollard joined the lab as an undergraduate neuroscience major in his sophomore year in 2019. Historically, the Jenkins Lab has focused its efforts on understanding male reproductive health and the role men play in the health of their offspring—topics seemingly unrelated to neurodegenerative diseases. Mechanistically, the lab is interested in understanding how environmental factors alter chemical markers on DNA. These markers, called methylations, control when and where genes are turned on (“expressed”). Examining where methylations are located on a piece of DNA can inform which genes are active, what tissue the DNA came from, and how healthy the tissue is.
This type of research requires extensive knowledge of bioinformatics and data analytics. “Once Chad joined the lab, he quickly became interested in the bioinformatics work,” says Timothy Jenkins, professor of physiology and head of the Jenkins male reproductive lab at BYU. “[Pollard] took my first bioinformatics class on DNA methylation and really fell in love with the computational side of things.” The knowledge and skills Pollard was gaining in the Jenkins Lab set him up for his big idea.
All cells to some degree release little fragments of their own DNA, called “cell-free DNA,” into their surroundings. The Jenkins Lab wanted to take pieces of cell-free DNA and try to identify the type of tissue the pieces came from by looking at their methylation marks. This technology, originally used to develop fertility tests that identify sperm in the male reproductive tract, has been repurposed for several different applications: cancer screening tests, sexual assault kits, and, now, Alzheimer’s disease diagnostics.
Around the time that the Jenkins Lab started using this new technology, Pollard was beginning his core neuroscience coursework as an undergraduate. He saw that the tools he was using in the lab for fertility tests could potentially be applied beyond sperm and reproduction—to the brain.
“I was in these classes, and they started talking about problems with diagnostics and neurodegeneration and the cellular pathways that are active when neurons die,” Pollard says. “That’s how Alzheimer’s and Parkinson’s diseases work—neurons die. I thought, I bet if we can identify little fragments of sperm DNA, we could do it with neuron DNA, too.”
Alzheimer's disease is the fifth-leading cause of death in U.S. adults 65 years and older and the sixth-leading cause of death in U.S. adults overall.
Normally, cell-free DNA from neurons in the brain remain confined to the brain, undetectable in the blood. However, some events—for example, cell death—massively increase the amount of cell-free DNA released into blood circulation. Pollard thought that he could indicate neurodegeneration by identifying the presence of neuron DNA in the blood.
Pollard initially worked on this idea on his own. Using publicly available data, he was able to detect neurodegeneration from cell-free DNA in the blood. On a whim Pollard entered his developing tech idea into BYU’s Big Jam Idea entrepreneurial competition in 2021, and he won first place. That’s when Pollard brought his idea to Jenkins, who encouraged him to submit it to BYU’s 2022 Student Innovator of the Year competition, where Pollard was also awarded first place.
After winning the competitions, networking, and taking Jenkins’s BIO-innovation class, Pollard was offered external funding to develop his diagnostic test. Pollard graduated from BYU in April 2022 and turned down a job in data analytics to take a position as a PhD student in the Jenkins Lab.
The next phase of Pollard’s Alzheimer’s research involves pinpointing where in the brain neurodegeneration is occurring. The brain is a heterogenous organ, meaning it contains many different brain regions, each with distinct functions. And what makes different brain regions and their respective functions distinct from each other is the types of neurons they contain.
There is currently no cure for Alzheimer's. Although there is one FDA-approved drug to slow the disease, its effectiveness is highly controversial.
For example, a region of the brain called the hippocampus, the brain’s memory center, contains neurons that have memory-specific functions. Another region called the motor cortex contains neurons that have movement-specific functions. Molecularly, this means different neurons have differences in gene expression and, therefore, differences in DNA methylation patterns.
“Now we’re learning that we can tell not only whether someone has neurodegeneration, but also what part of the brain it’s coming from, based on the neuron phenotype,” Pollard explains. For example, motor neuron DNA in the blood indicates ALS, while memory neuron DNA in the blood indicates Alzheimer’s disease or another form of neurodegenerative dementia.
“When we talk to experts in Alzheimer’s disease, they always say, ‘It’s so simple, but that makes total sense,’” says Pollard. It’s simple and non-invasive, requiring only a blood sample. “No one’s looked at it this way before.”
“The coolest thing is watching a student take an idea and add a whole new dimension to it,” says Jenkins. “For [Pollard’s] idea, we don’t know exactly where it’ll end up, but the idea is extraordinarily biologically sound and extremely simple. So, in theory, it should work.”
“Right now, the only way to diagnose someone is from their symptoms, which are detectable way down the road when it’s practically too late to stop the disease,” says Pollard. “Hopefully this can change things.”
Pollard and Jenkins have obtained a patent for their technology and cofounded a company, Renew Diagnostics, to continue pushing the limits of diagnostic medicine. Together, they hope to make a significant impact for the millions who suffer from Alzheimer’s and other diseases by identifying and ultimately slowing neurodegenerative disease.