Casey Cook, PhD, has a particular bent for jigsaw puzzles and isn’t afraid to admit that she keeps all of her finished puzzles. Being able to see how the pieces fit together is much like trying to find solutions to what causes disease: there is an art to figuring out how one research discovery leads to the next one.
The puzzle that Dr. Cook is determined to solve is how to cure Alzheimer’s disease. She joined the USF Health Morsani College of Medicine in May as an associate professor of Molecular Medicine to further advance her quest.
“I have had great-grandparents and grandparents with Alzheimer’s disease so I know the sadness and frustration it can cause,” Dr. Cook said. “Part of the motivation in my work is to change things with this disease. There have been many strides — and it’s exciting to try to be a part of making lives better.”
Dr. Cook is particularly intrigued by a type of immature cell in the brain called oligodendrocyte progenitor cells, or OPCs, and has research funding from the National Institutes of Health to study these cells and how learning more about them could reveal more about Alzheimer’s disease.
OPCs are a precursor to oligodendrocytes, cells which play a critical role in creating a protective layer of fat and protein called myelin in the brain. Myelin forms an insulating sheath around nerve cells, which helps electrical signals travel between neurons. This ultimately enables nerve cells to communicate better and the brain to work faster and with more flexibility.
But when this sheath is damaged, the brain develops what are called myelination defects.
“It’s understudied and not understood well,” Dr. Cook said. “Myelin is similar to insulation for neurons. You can use the analogy of insulation for electrical wires, facilitating speed of signaling. The myelination defects are creating interference, slowing the signaling speed and interfering with thought processes.”
Myelination defects are found within a number of neurological disorders, including Alzheimer’s. Trying to learn more about these defects brings Dr. Cook back to studying OPCs, which still possess the ability to regenerate.
“When you lose neurons, they are gone,” Dr. Cook said. “But OPCs have the ability to differentiate and form new cells. If we can understand OPCs, they may provide a new source for cells in the brain. We’re trying to understand why, when OPCs are in the brain, with their special properties, why don’t they protect against myelination defects?”
Dr. Cook also is doing genetic studies to evaluate how altering the expression of different genes within OPCs may change how the cell functions.
“We can also use genetic models to specifically change expression of different proteins within OPCs and then see if it provides protection against Alzheimer’s disease,” she explained.
Dr. Cook, who came to USF Health from the Mayo Clinic Jacksonville, also is using her NIH funding to study genetic variants of tau protein. This protein normally occurs in the brain and helps regulate the structure and function of neurons. In particular, tau is believed to play a crucial role in maintaining microtubules, which are likened to railroads of the cell and essential for transport.
However, in disease the tau protein can undergo harmful changes, becoming misfolded and accumulating into so-called ‘tangles’, which can damage or kill neurons and lead to cognitive decline and memory loss.
“We are studying a genetic variant that increases risk for both Alzheimer’s disease and the second most common form of dementia, known as Frontotemporal dementia. In particular, we hope to understand how this variant increases risk in order to ultimately provide protection,” she said.
Dr. Cook said there is good reason to feel optimism with Alzheimer’s disease research with the strides that have already been made — even in the years since she earned her undergraduate degrees in chemistry and psychology at Buena Vista University and her PhD in neuroscience from the Stritch School of Medicine at Loyola University Chicago.
“It has changed so much over the years,” she said. “An Alzheimer’s disease diagnosis for a loved one may be terrifying to family members, but an accurate diagnosis is absolutely critical to ensure people are enrolled in the studies and treatments that will be most beneficial.
“There are also new ways to look at monitoring of the disease course — available blood tests can provide a quick snapshot to indicate whether a drug may or may not be working,” she said. “There is a long way to go, but I call tell you there are many researchers working hard to change things.”
Like Dr. Cook.
— Photos by Freddie Coleman, USF Health Communications