Rowan researchers focus on Alzheimer's detection

Rowan researchers focus on Alzheimer's detection

by Kim Mulford, Courier-Post

STRATFORD — Someday, a medical exam could include a simple blood test to see if a patient has Alzheimer's disease 8 to 10 years before symptoms appear.

And if Bob Nagele and his team of eight fellow researchers at Rowan University School of Osteopathic Medicine have anything to say about it, that day is quickly drawing near.

Alzheimer's is the most common form of dementia, a term for memory loss and problems with thinking that affects daily life. People over age 65 are at greater risk, but about 5 percent have early-onset Alzheimer's, which strikes people in their 40s and 50s.

About 5.1 million Americans are affected by the disease, and that number is expected to swell by 40 percent over the next decade.

Even worse, according to the Alzheimer's Association, it is the country's only leading killer that cannot be prevented, cured or slowed down.

That is, so far.

Nagele's team is among those across the country racing to develop an early diagnostic test so scientists can find a way to slow Alzheimer's progression, perhaps through medication.

Researchers are looking for biomarkers that indicate the presence of the disease, including proteins in the blood and in cerebrospinal fluid, genetic risk profiling, and brain imaging. RowanSOM researchers are zeroing in on specific autoantibodies in the blood.

"We don't know who's going to be first," said Nagele, a RowanSOM professor and cell biologist. "We're working as hard as we can, as fast as we can."

For the Washington Township resident, it can't come soon enough. His own father has both Alzheimer's and Parkinson's disease. His maternal grandmother and two uncles died from Alzheimer's. His mother-in-law is in the end stages of Alzheimer's and hasn't recognized her daughter in years.

Cassandra DeMarshall of Mantua, a doctoral student at RowanSOM, is writing a scientific paper on the results of a pilot study the team conducted on 50 serum samples taken from people with mild cognitive impairments. The samples were collected by the Alzheimer's Disease Neuro Imaging Initiative. The team also tested 50 control samples taken from people without the disease.

The team expects to publish a paper within the next couple of months.

While the researchers can't announce their results publicly just yet, the study sought to determine how accurate the early diagnostic test could be, and how well it could differentiate between Alzheimer's disease and other kinds of brain diseases, such as Parkinson's and multiple sclerosis. About 40 percent of dementia is caused by other issues that can be addressed: side effects from medication, poor blood flow in the brain, and chronic depression.

The team thinks it has a viable diagnostic test on its hands, with an accuracy rate above 95 percent.

"We didn't know it would turn out to be this promising," said DeMarshall, who hopes the paper will attract more funding for a larger study, so the test can win FDA approval.

"This has definitely been a dream to work on something like this," she added.

Here's how Nagele explains the process:

The brain is covered with a protective barrier separating it from circulating blood and the fluid that nourishes and supports your brain. The barrier acts as a gatekeeper to maintain a constant environment in the brain. If the blood-brain barrier breaks down, it can develop tiny leaks that allow blood to seep in and kill brain cells called neurons.

Nagele thinks this is one of the triggers of Alzheimer's disease: Once the neurons die in the adult brain, they can't be replaced.

"Our theory, which seems to be holding true," said Nagele, "is that many of the neuro-degenerative diseases have one thing in common: The blood-brain barrier breaks down. The disease that we call it depends on where it happened."

Nagele and his research team already discovered that all human blood contains thousands of autoantibodies, which appear to clear away disease-associated debris that gets into the blood. If a disease attacks a certain organ of the body, the immune system cranks up and produces a specific type of autoantibody to clean up the mess. As the disease progresses and more tissue dies, more autoantibodies are produced.

Researchers think if they can figure out which autoantibodies — or biomarkers — correspond to which disease, they can nail down an early diagnostic test for any disease, be it Alzheimer's, Parkinson's, multiple sclerosis, or even breast cancer.

Nagele and his team are pursuing those hunches, too, in the school's new Biomarker Discovery Center at the New Jersey Institute for Successful Aging, and they have already submitted a paper on an early diagnostic test for Parkinson's. That work was funded by the Michael J. Fox Foundation.

To test the blood for specific autoantibodies, researchers take a drop of blood and smear it on a microarray, a one-inch by three-inch slide dotted with 23,500 tiny proteins, about a third of all proteins made in the human body. When scanned with a laser, the proteins light up in reaction to certain autoantibodies. The brighter the color, the more of that autoantibody is present.

"Not only can you detect the disease, but we're also able to distinguish early from later stages," Nagele said. "That's important because physicians are going to want to monitor the progress of their patient."

It takes between 10 and 12 hours to process and analyze one microarray, using a powerful computer. For this pilot study, which took about a month to complete, the team processed up to eight slides a day.

With additional research, the team can narrow down which proteins they need to focus on for each disease. That lowers the cost of each microarray, from $2,000 per slide to about $100.

And that drop of blood can come from just pricking a finger.

The pilot study on the early Alzheimer's test was funded by the Osteopathic Heritage Foundation, but the team needs to secure more funding to conduct a much larger verification study and perhaps win FDA approval to get the test on the market. Nagele estimates the cost to get a test approved for each disease is about $3 million. Nagele believes there is about a $3 billion market for an early diagnostic test for Alzheimer's.

"I know, for sure, I can complete the entire thing, including FDA approval, within one calendar year," Nagele said. "But it's possible only if you have the funding and financial resources to do it."

An early diagnostic test could help pharmaceutical companies test promising drugs earlier in the disease's progression, before it can wreak irreversible havoc in the brain, Nagele explained.

And an early diagnosis also helps patients plan for the future, and to join clinical trials on drugs that could slow or halt the disease, explained Claire Day, senior vice president of Alzheimer's Association Delaware Valley Chapter.

"It's really exciting and encouraging to know we're getting closer to detecting the disease more accurately and with precision, but we need those treatments (to slow progression) or a cure," Day said.

"We cannot wait."

Right now, patients can be diagnosed once they seek a medical explanation for memory loss and thinking problems, explained Dr. Carol Lippa, director of the Memory Disorders Program at Drexel University College of Medicine. Rarely, some people with a family history of Alzheimer's can be tested for certain genes. But people usually aren't tested until they start showing symptoms, usually in their 70s.

Still, Lippa sees a bright future for Alzheimer's research.

"We're in the home stretch of these studies that keep the toxic substances that cause the disease from building up," Lippa said. "I think we're going to see big changes in the next five years in our identification and intervention for the disease."

The brain disease has devastated Nagele's own family. Though his mother never developed the disease, he and his wife have watched her mother in decline. Given his family history, Nagele tests his own blood annually to see if his brain has started to succumb. So far, he, too, has been spared. But he does what he can to keep himself and his brain healthy.

In the meantime, he and his team focus on research they believe will make a difference.

"I feel like I have limited time in this world to do research," Nagele explained. "So I'm only going to work on what I think are big and important questions."

Additional Details:

Date Published: Sunday, March 29, 2015 - 11:00
Source URL: Rowan researchers focus on Alzheimer's detection