A Perfect Effort Against Alzheimer’s

Saturday, July 30, 2016

Rush Alzheimer’s Disease Center receives $14.3 million NIA grant renewal

By Kevin McKeough

The brains — more than 700 of them and counting — lie on the racks of 86 freezers and refrigerators in a securely locked, 3,600-square-foot facility in Rush University Medical Center’s research building. Once, each of them contained a person’s thoughts and feelings, memories and expectations, hopes and regrets. Each directed a man or woman’s actions and made decisions — including a decision to donate the brain itself to research after death.

Now each brain has been severed down the middle, slices from one hemisphere held in airtight, sealed plastic bags filled with protective fluid. The other hemispheres have been sliced into slabs and individually bagged before being packed into a special box and put in deep freeze. These carefully preserved biospecimens, as they’re called, are an invaluable resource for research in Alzheimer’s disease, both at Rush and worldwide.

For 25 years, the Rush Alzheimer’s Disease Core Center has been responsible for obtaining and preserving organ donors’ brains and making selective use of them in studies seeking to understand Alzheimer’s better. Throughout this time, the core center has received support from the National Institute on Aging, which just renewed the center’s grant funding, awarding it $14.3 million over the next five years.

The core center’s grant renewal application received a perfect score of 10, which essentially required that all 21 members of the NIA’s grant review committee award the application a perfect score.

“It’s a statement by our successful peers about what they think about the quality of work that we’re doing,” says David Bennett, MD, director of the Rush Alzheimer’s Disease Center and the Robert C. Borwell Professor of Neurological Sciences. (One of 29 NIA-funded Alzheimer’s centers nationwide, the core center is the largest part of the even larger Rush Alzheimer’s Disease Center, a clinical research center within Rush Medical College.)

“It shows that we still are central to the research that’s going on in Alzheimer’s disease, that after 25 years, what we’re doing still is tremendously important,” adds Julie Schneider, MD, professor of neurology and neuropathology and associate director of the Rush Alzheimer’s Disease Center.

‘This is a tough nut to crack’

Alzheimer’s disease is the most common cause of dementia, a condition that degrades cognitive functions such as reasoning, memory and judgment. The disease affects about 5.4 million people in the United States, according to the Alzheimer’s Association, which estimates that Alzheimer’s and other dementias will cost the U.S. $236 billion this year. A recently published paper by Rush researchers reported that Alzheimer’s contributes to more than 500,000 deaths annually, a rate comparable to heart disease and cancer.

“Alzheimer’s disease is a major cause of death, it’s a major cause of disability, it’s a major cause of economic hardship, family hardship,” Bennett says. “For most people, their thinking and their memories are about the most precious thing they have.”

The human brain has an extraordinary ability to rearrange neural connections as it learns and to adapt to injury. By the time Alzheimer’s dementia overwhelms that ability and begins robbing people of their thoughts and memories, the damage it has caused is so great that it has thwarted massive efforts to find a cure.

“It’s been more than a dozen years since the last drug was approved, and there have been about 450 failed clinical trials since then,” Bennett said. “This is a tough nut to crack.”

The research drawing on the core center’s resources focuses on disease prevention, hoping someday to spare the living from Alzheimer’s devastation. Without such advances, the number of people with Alzheimer’s in the U.S. is expected to increase to 13.8 million by 2050, the Alzheimer’s Association estimates.

Paradoxically, health improvements that have extended the lifespan also allow the disease a longer period of opportunity to develop. “Postponing death past the point where Alzheimer’s disease starts led to the rise of Alzheimer’s disease,” Bennett says. “Now we want to push Alzheimer’s disease to the other side of death.”

Resources found nowhere else

In seeking solutions to Alzheimer’s, Rush has gathered and deployed resources that literally aren’t available anywhere else in the world. The core center encompasses the ongoing, 23-year-old Religious Orders Study, which recruits and annually collects clinical information and biospecimens (blood, etc.) from older Catholic clergy (most past 65 years of age), including minorities. Religious Orders Study participants do not have a diagnosis of dementia upon their enrollment in the study (although some go on to develop it later), and they agree to donate their brains to the study upon their deaths.

The core center also includes the African American Clinical Core the Latino Core,which recruit and collect annual data from black and Latino participants without dementia, some of whom also agree to donate their brains upon death. “We know so much about white people and we don’t know much about pathology in Latinos and African Americans, and it may be different,” Schneider says.

The three studies have enrolled a combined total of more than 1,750 participants who have provided clinical information and biospecimens, and the programs have received more than 700 organ donations. (Another study within the larger Rush Alzheimer’s Disease Center, the Rush Memory And Aging Project, takes the same approach and has acquired brains, spinal cords, nerves and muscles from more than 650 deceased organ donors.)

“When the brains come in, we characterize them for a variety of common chronic diseases of aging, and we save them so we can go back later for other studies and share them with other researchers,” says Schneider, who oversees the process of obtaining and storing the core center’s biospecimens — including coordinating the harvesting of donors’ brains within hours of their deaths. The Rush investigators also use these donated organs to study stroke, Parkinson’s disease, and other degenerative diseases. 

‘Research that can’t be done any other way’

The Religious Orders Study and Rush Memory and Aging Project are the only two studies in the world in which all participants enroll without dementia, agree to be tested annually until death, and donate their brains and other organs for autopsy after death. The core center’s resources therefore provide researchers with unique and important opportunities. By examining tissue samples for the pathologic signs of Alzheimer’s and comparing them with the donor’s medical data, they can investigate the relationship between Alzheimer’s disease risk factors and the changes in the brain that lead to loss of cognition.

“Those biospecimens allow us to conduct all kinds of research that cannot be done any other way,” said Bennett, who is principle investigator of the Religious Orders Study. “We can see when the disease starts, we can track how fast the decline is, and we can look at the risk factors they had before they started declining and their effects when people did start declining.”

Researchers additionally can compare the data and neuropathology of people who died without ever developing Alzheimer’s with the same information about people who had the disease, an ability that is enormously useful for research related to disease prevention. For example, studies have found that higher levels of education don’t protect against the development of Alzheimer’s disease in the brain itself, but it helps delay the onset of the dementia the brain disease causes.

The core center also is remarkable for sharing its resources with researchers outside Rush, including more than a dozen strategic partner programs at other major academic medical centers across the USA and Canada, and other researchers worldwide. “We share blood and brain tissue and the data that we’re collecting with other people, and we’re happy for them to do their own studies,” Schneider says. “That’s unique, because within the NIH community it’s so competitive.”

Those researchers in turn share the data their studies generate with the core center to share as well. Just since January of 2011, Rush Alzheimer’s Disease Center researchers have published around 400 papers in peer-reviewed journals. “We are piggybacking on each other’s work,” Bennett says.

All of it is made possible by the people, both living and deceased, who agreed to share some of their bodies and, most precious of all, parts of their remaining days. Bennett and Schneider say they’re indebted the thousands of study participants and their families who follow through on the organ donation.

“It’s amazing when you think about the older people who participate and how altruistic they are,” Schneider says. “We’re always coming to them with new questionnaires and new gadgets to test them, and they give incredibly of their time.”

The Rush Alzheimer’s Disease Center is grateful for the generous support of the National Institutes for Health. You can learn more about the studies and data generated by the Rush Alzheimer’s Disease Center by visiting www.radc.rush.edu.