Alzheimer’s Disease: No Stone Unturned
In terms of clinical care and clinical research around Alzheimer’s disease, URMC has a robust history of serving nearly 100,000 affected individuals in the Finger Lakes region.
“We are a regional center for providing Alzheimer’s diagnosis, care and support to patients and their loved ones, and that’s something to be very proud of,” says Neuroscience vice chair Kerry O’Banion, MD, PhD, who is working to bring together scientists across the University to elevate the understanding of the disease from a host of perspectives. “But the amount of clinical research we’re doing far outweighs the amount of basic research we’re doing to identify the underlying disease causes. That’s what we’re hoping to change.”
O’Banion says the scientific community has slowly dispelled the long-held hypothesis that amyloids (plaques) in the brain are the sole culprits of the disease. Although amyloid accumulation is an indicator, scientists agree there are more complex causes at work.
“About 80% of research dollars have gone to studying whether preventing amyloid accumulation will prevent Alzheimer’s, but the promise has not really unfolded,” says O’Banion, who believes more focus is needed on resilience to aging and how memory ability changes with age.
“We need more work in model systems of the disease, in mice for example, that looks at how connections are lost, because it’s a disease in which the brain is disconnecting within itself,” says O’Banion, adding that Alzheimer’s pathology begins 20 years before the first symptoms appear. “The neurons aren’t firing as they should be. As different parts of the brain are affected, cognition disappears. Recovering what is lost is unlikely something we will be able to do in the near future, but preventing the loss has become a clear target, and is within our reach.”
Accomplishing this means gaining more insight into disease progression, and the fundamental changes that happen early, so that people at risk can be identified earlier and potential targets for intervention—blood or spinal fluid for example—can be explored.
“We have a fairly good handle on patient populations and some really cool tools to start to look at this harder,” he says. “But then, how do you use that information to shift the balance in a positive way? There may be a drug shown to slow the process in an animal model, but to find out why it works and whether it can be translated to humans, you need to look at it from a mechanistic standpoint. That’s biochemistry, pharmacology, therapeutics. But you also have to consider behavioral therapy as just as important. For example, social engagement may be key to maintaining memory.”
Alzheimer’s has so many facets, he says, no scientific stone can be left unturned.
“What happens is that every researcher picks their favorite and concentrates on it,” says O’Banion, who is meeting with every UR scientist involved in Alzheimer’s and dementia-related work—including Psychiatry, Geriatrics, the School of Nursing and elsewhere—to collect ideas and reimagine a broad, collective research approach. “You can’t ignore anything. People who may be working more in the weeds, so to speak, are just as vital as those in leadership.”
A molecular neurobiologist, O’Banion was one of the first in the country to study
the link between neuro-inflammation in the brain and the pathogenesis of Alzheimer’s and other brain diseases. His laboratory with this focus has been externally-funded for more than 20 years.
“The longstanding dogma was that inflammation in the brain was bad, and that if you could slow the inflammation you slow the disease,” he says. “But over the last 10 years, our research using mouse models shows inflammation might actually be very beneficial. So we’re trying to hammer that out by looking at amyloid pathology and cognitive changes. There’s a ton of potential here.”
O’Banion says UR researchers are also gaining insight—through animal models and at the cellular level—into the mechanisms by which neurons talk with each other, and how synapses are formed and lost. These studies could potentially be meshed with Foxe’s clinical research in EEG brain mapping, he believes.
Numerous experts in neurology are also studying the roles of energy balance and oxidative stress (the damage to mitochondria during energy creation) in neuromuscular diseases.
“Understanding how to be more efficient with energy or help mitochondria deal with stress is key,” he says. “And what’s really interesting is the connection between inflammation and oxidative stress, which together contribute to the aging process. There’s something there, and people are working hard on it.”