UK program takes healthy, unhealthy brains in hopes of finding treatment for Alzheimer’s

Wilson Yates “had a very good brain,” as his wife put it.

 

He graduated from the prestigious and selective Citadel military college and became a lieutenant in the Air Force. He earned his law degree from the University of Virginia and served as vice president and counsel for Kentucky Central Life Insurance.

 

Ultimately, though, it was his brain that led his family to put him in a nursing home, but it’s his brain that will also hopefully help others — people who have Alzheimer’s disease like he did.

 

Yates’s wife, Isabel, donated his brain to University of Kentucky’s Alzheimer’s Disease Center when he died in 1997, making his brain one of the roughly 1,000 that have been collected by the center since the mid-1980s.

 

Isabel Yates, 86, also hopes to add her brain to the bunch. She does not have Alzheimer’s but enrolled as one of the “healthy brain aging volunteers,” as the center calls them, whose brains are used as controls in studies.

 

“I can feel for those people. We hope and hope for them to get better, but they’re only going to get worse,” said Yates, who is a former Lexington vice mayor and councilwoman. “That’s my children (who are now at risk to get this.) It’s a real concern.”

 

Both types of brains will be needed to understand “this nasty thing called Alzheimer’s disease,” and UK researchers have made inroads through the brain donation program, said Stephen Scheff, associate director of UK’s Sanders-Brown Center on Aging, which the Alzheimer’s Disease Center is a part of.

 

And if advancements toward slowing the disease’s progression — or even a cure — are to be found, researchers hope it will be done with the help of programs like the one at UK.

 

“You can’t do this disease in isolation,” Scheff said. “It’s too complicated. You need to head it from multiple fronts.”

 

Buckshot for brains

 

Dr. Peter Nelson slips a slide into a microscope. The computer connected to the microscope shows a grayish background with a few, small, darker specks dotting the screen.

 

“There’s essentially nothing there,” said Nelson, director of UK’s neuropathology division. “And this is a part of the brain that’s not affected by Alzheimer’s disease.”

 

He then pulls up an image that looks as if buckshot had been shot through the slide. Black holes riddle the image along with larger, darker gray blobs.

 

The holes are neurofibrillary tangles — “rope-like fibers” that move out healthy parts of brain cells until the cells die — and the blobs are pockets of amyloid plaque, protein fragments that a healthy brain would break down, Nelson said.

 

Alzheimer’s disease, the most common form of dementia, gets worse over time as the brain cells degenerate and die, causing a steady decline in memory and mental function.

 

“Your brain rotting is away,” Scheff explained later. “That’s basically what’s going on.”

 

The slide is just one sliver from one of the brains in the bank. One brain can yield more than 100 pieces to study, Nelson said.

 

UK started collecting brains after it became one of 10 original universities to receive funding from the National Institutes of Health in 1985 to create a brain bank.

 

The program enrolls people with neurological diseases, like Alzheimer’s, and healthy people who are age 70 and over. Residents of all genders, racial backgrounds and ethnicities are encouraged to take part.

 

Participants come in once a year for a three hours’ worth of physical and cognitive tests that involve brain teasers and lifestyle questions, among other things. And when they die, their loved ones or doctors call the researchers so they can perform an autopsy and remove the brain.

 

“It enables us to do things that no one else can do,” Nelson said of having the bank. “All those big boys with all those big buildings (at other schools), they cannot do what we do there.”

 

And the removal of the brain happens very soon after death.

 

It’s not uncommon for Nelson or Scheff to receive a call at 2:30 a.m. that one of their participants has died. And usually within two to three hours, they complete the autopsy, which is important because the brain rapidly changes after death.

 

“That enables us to answer questions related to brain biochemistry that nobody else can do,” Nelson said.

 

Researchers remove brains from the back of participants’ heads, which means the participant can still be viewed at the funeral.

 

“We’re performing autopsies that are trying to get us information for curing these darn diseases, but it’s something that we do in the spirit of deep respect,” he said. “There’s a real gravity to it. These are people. These are human beings.”

 

Five hundred people with no cognitive impairment and roughly 300 people with diseases, like Alzheimer’s, have agreed to donate their brains when they die, said Dr. Greg Jicha, the clinical care director for the program. And out of that group, 40 to 50 people usually die a year.

 

“We have people who enrolled at that time (the 1980s), and they are still coming to visit us,” he said. “Seventy is the new middle age.”

 

After looking through the microscope, Nelson walks across the lab and pulls a brain out of a round plastic container.

 

The grayish beige organ does not look atrophied, which means it came from one of the participants without cognitive deficiencies — a 95-year-old to be exact.

 

“Probably the most amazing single thing in the universe that I know of is right here in the palm of my hands,” he said. “This underscores the fact that many people live healthy lives well into their 90s without degradation of their capacity to learn and remember.

 

“And I think that’s inspirational to all of us to try to learn what can make it so it’s not an inevitable form of aging.”

 

Spotting it earlier

 

And like language and complex thinking, Alzheimer’s is only seen in humans. No other animals suffer from this disease.

 

“The human brain is what separates us, makes us different, and it’s qualitatively more complex than the others,” Nelson said. “And in order to achieve that level of complexity, you have to develop new things that may have a dark side.”

 

This makes the brain bank all the more essential for research, said Linda Van Eldik, director of the Sanders-Brown Center on Aging. Besides human tissue, researchers have used brain cells grown in cultures or mice that have been manipulated to show symptoms of the disease.

 

“But you can ask the important research questions … and actually look in human tissue to know whether it’s happening in the brain of Alzheimer’s or not,” she said. “It’s always nice to go back to the real human disease and ask those questions.”

 

And by having those samples, researchers can follow the progression of the disease and potentially notice changes that occur before the onset of symptoms.

 

“We have this rich database of cognitive and medical information on these folks … all this longitudinal information of how the disease progresses, and we also have the brains, so we can correlate the very earliest changes that occur,” Van Eldik said.

 

The researchers have noticed brains that showed signs of Alzheimer’s — the tangles and plaque — yet the patient had not displayed changes in cognitive ability. This has opened a new category of diagnosis called “pre-clinical” Alzheimer’s.

 

“So we’re defining these very earliest transitions that occur in the brain and trying to use that information … to try to come up with potential new drug targets or new areas where we can translate that into interventions,” she said.

 

Researchers and doctors have to learn how to intervene earlier. “It’s a lot more difficult to reverse damage that’s already happened in the brain than preventing it in the first place or slowing it down,” Van Eldik added.

 

This issue has also opened up ethical issues that researchers will have to navigate, they said.

 

“The problem is if in fact that disease starts, let’s say, in your 30s, but you’re neurologically normal,” Scheff said. “You get this information, and every time you start forgetting something, you’re like, ‘Am I starting to have the disease now? Is it setting in?’ Now you’re second guessing yourself on everything.”

 

What’s next

 

The largest, most recent impacts in fighting Alzheimer’s will likely be seen in ways to detect it earlier and slow it down, they said.

 

Researchers also likely won’t find a single way to fight the disease, but the eventual treatment will be a cocktail of therapies to attack the different components, much like with HIV, Van Eldik said.

 

“The interesting thing about the brain is it has no obligation to simplicity,” Nelson said.

 

Researchers with the Alzheimer’s Disease Center have also spent time dispelling misconceptions. Many people think that Alzheimer’s is an eventuality of aging, which is incorrect. Some medicines are already available that can slow the disease if it’s caught early enough, they said.

 

“It’s not from aluminum,” Scheff added. “Our center debunked that.”

 

But they also can’t point to the cause of Alzheimer’s — another big unknown they are trying to tackle.

 

“It’s turning out there may not be one single beginning problem,” Van Eldik said. “It may be that as we age, we become more vulnerable to a lot of different insults.”

 

Yates hopes that soon the researchers will have more answers than questions.

 

Her father lived to be 103, retiring from medicine at age 95, and never lost his wit. Yates, who helped the Sanders-Brown Center on Aging raise money and open, “knows what successful aging is” and wants to see more people accomplish it.

 

When her husband was diagnosed, Alzheimer’s “wasn’t the household word it is today. It’s something people dreaded,” she said. “I don’t want more people to have to go through what we did.”

 

____________________________

 

UK’s Sanders-Brown Center on Aging has more information on how to take part in the brain donation program.