Twenty years ago, Terrence Town, Ph.D., professor of physiology and biophysics at Keck School of Medicine bet his career on a hunch.
When Town began looking at links between Alzheimer's disease and the immune system, most people in the field dismissed his research. Alzheimer's was still poorly understood, and there was little evidence to back him up.
"I absolutely could have been barking up the wrong tree," he says.
That tree seems to have borne fruit. While theories about the immune system were rejected when Town started his research in the 1990s, inflammation, characterized by a buildup of plaque in the brain, has since been identified as a key player in Alzheimer's disease.
Fueled by a growing awareness about Alzheimer's, as well as new medical technology, research has rapidly yielded discoveries about the disease. Scientists have uncovered the biological processes involved, identified genes and lifestyle factors that put people at risk, plus they've revealed the way in which the disease progresses and discovered the pathology of the disease begins long before symptoms appear.
What has eluded scientists so far is an effective treatment. But the researchers and physicians at Keck Medicine of USC believe a breakthrough is near. They're pushing forward to find therapies that are going to finally change the course of care for the millions of Americans who suffer from Alzheimer's disease.
Today, 5.3 million Americans have Alzheimer's disease — the most common form of dementia that is irreversible and causes problems with memory, thinking and behavior.
Understanding the Brain
Another pioneer in Alzheimer's disease research is Berislav V. Zlokovic, M.D., Ph.D., whose research has illuminated the role that blood vessels in the brain play in the development of dementia.
Zlokovic, professor and chair of the Department of Physiology and Biophysics at Keck School of Medicine, first proposed more than 20 years ago that flaws in the blood-brain barrier, which keeps potentially dangerous foreign substances from moving from blood vessels into brain tissue, underlie all cognitive disorders, including Alzheimer's disease.
For decades, Zlokovic and his research team have made significant advances in understanding the blood-brain barrier and its role in Alzheimer's. Several of his discoveries have already contributed to the development of clinical trials for Alzheimer's disease, and he continues to make new discoveries.
There is now significant evidence that vascular dysfunction is an early event in Alzheimer's disease. Zlokovic's latest round of discoveries has unveiled many potential targets for novel treatments, and he continues to investigate treatment efforts of his earlier studies. Meanwhile, Zlokovic has also embarked on the hunt for biomarkers in blood and cerebrospinal fluid that he hopes can predict the onset of Alzheimer's disease 10 to 15 years before patients exhibit symptoms. This would be a huge advance in the field, since Alzheimer's diagnosis is currently triggered with the onset of symptoms. Zlokovic added that the pace of discovery has been aided by an explosion of medical technology that has helped researchers better understand Alzheimer's.
"Advanced technology — imaging and genetics — is very important in Alzheimer's research," Zlokovic says. "There are currently gaps in knowledge, but technology is helping us address important questions and is getting us there faster."
Picturing the Brain
Powerful new technology in the field of brain imaging is helping to advance understanding of Alzheimer's disease by finally giving researchers the ability to track changes in the living brain. Paul Thompson, Ph.D., professor of neurology, psychiatry, radiology, engineering and ophthalmology at USC, joined the university in 2013 and brought with him 20 years of brain-mapping experience.
About 15 years ago, Thompson's research first revealed the manner in which Alzheimer's progresses. "It is an odd disease because it sweeps through the brain like a forest fire," he says, adding that imaging showed it first attacks the memory center, then leapfrogs to the emotion centers and later hits the frontal lobes, which are involved in planning and self-control.
Thompson notes that advanced imaging techniques have also made it simpler and less costly for researchers doing clinical trials to evaluate the efficacy of a treatment. "It can make drug trials much less expensive, and we won't have to wait three to five years to figure out if something is effective," he says.
Treating the Brain
In the case of Alzheimer's disease, the research taking place at Keck Medicine of USC helped the medical center's doctors give patients the best possible care. The physicians have access to the latest information, as well as cutting-edge technology, to help patients as best they can.
Several clinical trials are underway through the USC Alzheimer's Disease Research Center to test investigational drugs. Some of the drugs being tested are aimed at improving the cognitive function of patients with mild or moderate Alzheimer's disease, or slowing the progression of the disease.
One trial tests a type of immunotherapy in patients at high risk of developing Alzheimer's, but who haven't experienced the onset of symptoms; another early phase trial assesses a neuroregenerative compound. The Alzheimer's Disease Research Center is also participating in a neuroimaging study funded by the National Institutes of Health that will take brain images, as well as biomarker measures, to track changes in the living brain over time.
"We are committed to giving our patients the highest quality of care," says Helena Chang Chui, M.D., chair of the Department of Neurology. "Our practice benefits by having access to top researchers in the field who are finding ways to better diagnose and treat Alzheimer's disease."
That's The Keck Effect — more breakthrough treatments to help you make more memories.