TL1 Postdoctoral Training Program Spotlight: Aaron Smith Ph.D., RD, University of Kansas Medical Center

Project Title: Muscle-Brain Axis Biomarkers as Therapeutic Targets in Alzheimer's Disease

Project Summary: My project leverages my background in nutrition and clinical trials to explore an emerging, under-investigated target in Alzheimer’s disease neuromuscular function. By examining whether creatine monohydrate supplementation improves neuromuscular junction integrity—and how changes in neuromuscular junction function relate to AD biomarkers and cognition—this work will generate novel pilot data while equipping me with specialized training in clinical trials focused on aging, neuromuscular physiology, and lab-based assessments. Ultimately, this TL1 award positions me to become an independent investigator at the forefront of neuromuscular physiology and aging, laying the groundwork for larger-scale trials aimed at mitigating AD risk through improvements in neuromuscular function.

Mentors: Matthew Taylor, Ph.D., RD and John Thyfault, Ph.D.

Aaron Smith, Ph.D., is about six months removed from graduating with his Ph.D., with one of his career goals being to become an independent researcher in neuromuscular physiology and aging.

“Applying for Frontiers TL1 program has really provide that critical bridge to give me the time and the opportunity to train in the techniques I need to learn to become an independent researcher,” Smith said. “In addition to funding, this was an amazing opportunity to work with all the incredible mentors and Frontiers, and to bring my mentoring team together to work on this project.”

And one of his mentors, Matthew Taylor, Ph.D., studies nutrition and metabolism interventions that may improve mitochondrial function in people with Alzheimer’s Disease.

“Matt is studying both nutrition interventions and dietary supplements on mitochondrial function in Alzheimer’s,” he said. “I have gotten a lot of exposure to people with Alzheimer’s disease and trials and bringing it back to the skeletal muscle. One of the things we have seen is that before diagnosis and is that these patients are seeing the loss of skeletal muscle mass and well as muscle function.

“So, my project is studying to see if something that proceeds cognitive decline and diagnosis is neuromuscular function and how it may be impacted.”

And as Smith looks at a connection between skeletal muscle and brain health in Alzheimer’s patients, he is also seeing if there could be lifestyle interventions that could potentially positively impact Alzheimer’s patients.

“There is a marker called the neuromuscular junction and that’s the connection between the neuron, which is giving a signal to the skeletal muscle to contract, and in Alzheimer’s patients, there is a breakdown,” Smith said. “We recently conducted an ELISA (enzyme-linked immunosorbent assay) kit on people with Alzheimer’s to see if there are elevations in the marker that is at the neuromuscular junction.”

And while in ageing there is a natural breakdown, patients with Alzheimer’s may see that breakdown happen at an accelerated pace. And the dietary supplement creatine monohydrate has been shown to improve skeletal muscle mass and strength in various populations, but it has not been studied in patients with Alzheimer’s. Thus, Smith’s work aims to fill this gap.

As part of his project, Smith is also studying the biomarker phosphorylated-Tau (pTau 217), a blood biomarker that associates strongly with Tau in the brain. Tau is a downstream pathological hallmark seen in Alzheimer’s that leads to neurodegeneration.   Smith aims to see if the creatine monohydrate intervention associates with improvements in pTau217 in Alzheimer’s. He is also interested if changes in neuromuscular function and cognition associate with improvements in blood levels of pTau217.

As Smith continues to work on his project, the TL1 program has also helped him with a number of other resources and services.

“It’s great having access to network of people from grant writing to stats that have really made a difference in the way I approach things,” Smith said. “It has been great getting feedback from them and helped me think about how they can help me in the future as well. Meeting with my Frontiers mentors, Jake Sosnoff, Ph.D., and Holly Zink Ph.D. have really helped me think about what I need to do to get to the next place. Heather Fielding-Gebhardt, Ph.D., has helped me with scientific writing. It really is a fantastic opportunity.”