In the last years of his life, Bryan Spangelo's grandfather always kept family pictures by his bedside. They weren't simply snapshots of loved ones; they were a record of a life he had trouble remembering. "He needed those pictures in front of him to know that he had kids," Spangelo says. "You know, for most people there's nothing more important than their memories. It's their identity. It's who they are."
Spangelo's grandfather was diagnosed as senile, more a condition than a disease, but today would likely be diagnosed with Alzheimer's disease. Though time has lead to an improved diagnosis, many questions still remain about the disease that affects an estimated 4.5 million Americans.
A chemistry professor at UNLV, Spangelo is focusing on an essential question: What chemical processes in the brain are involved in the onset of Alzheimer's disease? Though Alzheimer's was first described a century ago — as would be expected, by Dr. Alois Alzheimer — much about the disease remains a mystery. "We know kind of what's happening during the disease. We know the hallmarks and features of it," Spangelo says. "But we still don't know how it's initiated, and therefore we don't know how to treat it. I want to know how it begins."
The National Institute of Neurological Disorders and Stroke awarded Spangelo a $221,750 grant for a three-year investigation into the neurological mechanisms associated with neuroinflammation, a condition which destroys neurons and is a hallmark symptom of the disease. of the disease.
Spangelo has zeroed in on the role of a particular neurotransmitter — a chemical that transmits signals between nerve cells — in preventing the progression of neuroinflammation. The research appears promising, and he says his lab is the only one in the country he knows of that is currently studying this approach.
Previous research had shown that the levels of the neurotransmitter GABA fall as Alzheimer's disease takes off. "GABA is the major inhibitory neurotransmitter in the brain. Its sole function is to stop things from happening."
To understand the role of GABA, a review of basic brain chemistry is useful. Spangelo describes two types of brain cells: neurons and astrocytes. Neurons are the information conductors. Astrocytes act as support cells to keep neurons working. But, in the case of Alzheimer's disease, the support system malfunctions. Astrocytes become activated and start releasing products that lead to neuroinflammation and the destruction of neurons. One of those destructive products is a small protein called interleukin-1, which further excites astrocytes.
In research presented two years ago, Spangelo established for the first time that GABA suppresses some of the activity of the interleukin-1 protein. Spangelo believes GABA works as a "physiological brake" on what is otherwise the runaway process of neuroinflammation. He is using his grant to further that research and study exactly how GABA slows the process.
"If we could figure out exactly what the mechanism is behind GABA, then we could start thinking about interventional therapy, what sort of drug might do the same thing and help prevent neuroinflammation," Spangelo says. "I'm looking for anything that gives us clues as to how the disease progresses."
By finding answers to the right research questions, Spangelo hopes to help improve the quality of those additional years.
As the Baby Boomer generation ages and people live longer lives, Spangelo believes the need for treatments of Alzheimer's disease and other chronic neurological disorders will only become more acute. "Diseases of aging are problematic right now," Spangelo says. "We're having a problem with adding years to people's lives but not really making them effective years."
