Zombie cells could be key to Alzheimer's susceptibility
The National Institute on Aging has awarded a Michigan State University College of Human Medicine professor a nearly $3 million grant to study how aging increases the risk of developing Alzheimer’s disease and to investigate treatments that could delay or prevent it.
“The biggest risk factor for Alzheimer’s disease is age,” said Marcia Gordon, the study’s primary investigator and a professor of translational science and molecular medicine. “I’m trying to understand what it is about the old brain that makes it more susceptible to Alzheimer’s.”
The answer, she believes, lies in senescent cells – those that are old, still alive, but no longer capable of dividing.
“Some people call them zombie cells,” Gordon said. “These cells stop performing their normal functions and begin to send out signals that likely trigger adverse changes in the brain, including the clumping of the beta-amyloid protein and tangles of another called tau.”
Of the estimated 5.7 million Americans who have Alzheimer’s, 5.5 million are over the age of 65, according to the Alzheimer’s Association. Ten percent of people over the age of 65 have Alzheimer’s, the most common form of dementia. By age 85, the rate rises to 40 percent.
“We think that if we slow down the biological aging of brain cells, we will slow the rate of disease progression,” Gordon said.
Under the five-year grant, she will look at ways to delay this biological aging and deplete the number of senescent cells. Possible treatments include restricting calories, which previous research has shown is associated with longevity. Rapamycin, a drug commonly prescribed for immunosuppression in organ transplant patients, also has shown some promise of extending lifespan.
Co-investigators on the study include colleagues Scott Counts, associate professor, and David Morgan, professor, in the Department of Translational Science and Molecular Medicine. Counts will obtain brain tissue samples donated by deceased Alzheimer’s patients and, using an advanced technique called laser capture microscopy, will look for biomarkers to identify senescent cells.
The possible link between senescent cells and Alzheimer’s is a relatively new area of research.
“I’m lucky to be on the forefront of it,” Gordon said.
Morgan, who will help analyze data, concedes he was skeptical when he first heard senescent cells mentioned as a possible contributor to Alzheimer’s.
“I thought that was a pretty odd approach,” he said, but “increasingly I’ve seen more and more data that’s supportive of this approach.”
Currently, there is no cure or effective treatment for the disease.
“We’ve got to think outside the box if we’re going to do something about Alzheimer’s,” Morgan said.
The goal of the study is not to find the fountain of youth, Gordon said, or even to cure Alzheimer’s. Few diseases that have been largely eradicated, including smallpox, were not cured, but have been prevented, she noted.
“It would be wonderful if we found a cure,” Gordon said. “But it’s much easier to prevent a disease than to treat it once you get it.”