The New War on Alzheimer's
By Laura Freeman
UAB Alzheimer's Disease Center Advances On Multiple Fronts
Jim Freeman survived D-Day. He survived Rommel's tanks rolling over his foxhole in North Africa, and even made it home after lying wounded in the snow at the Battle of the Bulge.
He didn't want his memories to burden his family. It wasn't until he was fighting his last battle in a war he couldn't win that he began to tell his stories, hoping someone would remember. War had taken all but one of his friends. Now Alzheimer's was taking everything else.
At 19, the boy from Alabama braved machine guns on Omaha Beach to cut barbed wire and free his squad from the killing zone. Now, family dinners were frightening. An echo of the person he had been, his struggle to follow the conversation and to seem like the same Uncle Jim brought him and everyone at the table near to tears.
Dying from Alzheimer's is like falling off a cliff in slow motion. It inflicts terrible collateral damage, taking not only the life of the patient but also the lives caretakers might have lived. In an aging society where the risk of Alzheimer's doubles every five years after age 60, the financial and social impact on the nation are becoming overwhelming. To counter this threat, federal resources have been mobilized in a campaign to fight Alzheimer's on multiple fronts.
Eirk Roverson, MD, PhD
Home base for that effort in Alabama is UAB's Alzheimer's Disease Center, allied with the Center for Neurodegeneration and Experimental Therapeutics (CNET). Director Erik Roberson, MD, PhD, oversees research into the neurobiology of how Alzheimer's develops and progresses. He works closely with Clinical Core Director David Geldmacher, MD, who leads care and research teams working to improve strategies for managing Alzheimer's.
Several clinical trials are underway, testing new interventions aimed at easing symptoms and slowing progression of the disease. To assist caregivers, a new training program is now available using telemedicine. A key observational study now recruiting will follow subjects who aren't yet showing symptoms of Alzheimer's to learn more about how the disease develops, identify new targets for intervention and learn how the disease is different in the south.
"Most of what we know about Alzheimer's is based on research conducted outside the south, and a particular problem is that very few African Americans have been included in previous studies," Roberson said. "The south has high rates of diabetes, obesity, and cardiovascular disorders including hypertension--all of which have a strong association with risk for Alzheimer's Disease."
Geldmacher said, "African Americans are about twice as likely to develop Alzheimer's Disease, and they seem to respond to risk factors differently. So far, around 30 genes have been linked to the risk for developing the disease. The strongest link is to APOE4, but this gene doesn't seem to have as great an effect in African Americans. We don't know if other genes are protective or if different factors are involved. We don't understand why because we haven't had enough African Americans involved in studies."
The APOE4 gene is more common in some areas of Africa, like Nigeria, but rates of Alzheimer's are lower. This could be because obesity and diabetes rates are lower and nutrition and exercise habits are different. The UAB study will look at how these factors and others may influence the causes of the disease.
"Our goal is to recruit about 50 percent African Americans in our study so we can make a meaningful comparison of how risk factors are expressed in different gene pools," Geldmacher said. "In the past, Alzheimer's was something we diagnosed after symptoms occurred. By then, too many brain cells were damaged for us to do much to intervene. Now advances in imaging and molecular medicine allow us to see earlier changes that can begin as much as 15 years before cognitive symptoms are obvious. If we can identify ways to influence epigenetic changes and targets for pharmaceutical and other interventions, we may be able to stop or slow the damage before it happens."
Participants in the study will have imaging studies, blood and genetic testing, and optional spinal fluid collection, which will be followed by an annual evaluation to detect changes.
"With imaging, we can see the accumulation of amyloid plaques and tau tangles," Roberson said. "The extent of these changes and where they show up in the brain tends to correlate closely with the degree and type of symptoms patients experience as the disease progresses."
Much of Roberson's research is focused on learning more about the tau protein and its role in the development of tau tangles and interaction with amyloid plaques.
"Early in the disease, the presence of tau protein seems to cause hyperexcitability of brain cells which can result in subclinical seizures. If we can reduce the level of tau protein, we may be able to reduce the hyperexcitablity and prevent the damage it seems to do," Roberson said.
Risk assessment is another clinical service available through the Alzheimer's Disease Center.
"People who have a family history of Alzheimer's or other concerns can come to the clinic for a risk assessment based on genetics and their health history, and they can have imaging studies to determine whether any changes are visible," Geldmacher said. "For many, this offers the peace of mind of knowing there are no signs of the disease. If changes are present, though we have no definitive therapies yet, we can begin early work to control other health issues that seem to influence risk, such as blood sugar, obesity and hypertension.
"The risk assessment, unfortunately, isn't usually covered by insurance, which brings into play another disparity on who gets Alzheimer's. Those who can't afford an assessment are also less likely to understand the role a healthy lifestyle plays in minimizing risks.
"We're hoping that what we learn about the disease over the next few years will lead to new ways we can help everyone who is at risk."
Erik Roberson, MD, PhD, Director of UAB's Alzheimer's Disease Center