Andrea Kelley prepares to show samples of beta amyloid plaques that contribute to Alzheimer's disease. Credit: Roseanna Garza / San Antonio Report

Research from the University of Texas at San Antonio suggests that the plaques that cause the symptoms of Alzheimer’s disease may be more complicated than previously believed, a finding that could significantly affect drug development for the disease.

Researchers found that in addition to the sticky proteins called amyloid beta, other neural and repair proteins also exist within the plaques, indicating new biomarkers for the disease that affects more than 5 million people in the United States.

Using imaging mass spectrometry, a technique used to produce a chemical snapshot of the distribution of molecules in a sample, researchers identified the components of fragments and decaying plaques found in the brain’s grey matter of people with Alzheimer’s.

Andrea Kelley, UTSA post-doctoral fellow in chemistry and principal researcher for the study, told the Rivard Report that her team discovered the different types of proteins unexpectedly.

“We were interested in using mass spectrometry to look at what else might be in these plaques, just to try it out,” Kelley said. “The identification of these additional proteins shows that there is really a lot more to these little plaques than amyloid beta.”

The neurological damage that accompanies Alzheimer’s is thought to be caused by amyloid beta, which are normally found in the membrane around nerve cells. But when amyloid beta clumps together it can kill the cells, impairing brain function.

Kelley explained that the majority of drugs aimed at treating Alzheimer’s focus on the reduction of toxic amyloid beta, but clinical trials of the pharmacological interventions addressing amyloid beta have largely proven unsuccessful, meaning that the disease is not well understood.

Alzheimer’s disease ranks as the sixth-leading cause of death in the country, according to the Centers for Disease Control and Prevention. By 2050, the number of affected people is expected to nearly triple, to 14 million.

Scientists do not yet fully understand what causes Alzheimer’s disease, but have known about the amyloid beta fibers since Alois Alzheimer found them in the brain of a German woman suffering from early dementia in 1901. Since then, the amyloid beta theory has been at the center of both treatment and research.

Advances in technology are giving Alzheimer’s research new potential, said Dr. Rong Zhang, a researcher at the Alzheimer’s Disease Center at UT Southwestern Medical Center.

“With this new technology you can see something that you [could not] see with conventional technology,” which gives researchers the opportunity to explore and develop new treatments, Zhang said. “This is a very complicated disease and it’s important that there are a lot of scientists from all over the world working on challenging [it].”

He said that the next step would be for researchers to examine what the proteins are doing, where they are coming from, and what their functions are within the molecular structure of the plaques.

Kelley said that while her research is still in its early stages, the findings serve as a good starting point for developing new a new focus for research to include the new biomarkers for amyloid beta, which may eventually lead to new drug targets.

Currently, only five drugs are approved by the Food and Drug Administration for the treatment of Alzheimer’s, and only three drugs have been approved in the last 14 years.

A study in 2014 found that 99.6 percent of all drug tested in clinical trials between 2002 and 2012 on Alzheimer’s had failed. The success rate was “among the lowest found in any therapeutic area,” the researchers concluded.

In January, after spending billions on failed drug trials, drug giant Pfizer gave up and pulled out of Alzheimer’s research altogether.

In the absence of a known cause or cure, the CDC estimates the cost of treating the disease was projected to range from $159 million and $215 billion in 2010, and could rise to $500 billion by 2040.

UTSA chemistry professor Stephen Bach, who specializes in Alzheimer’s research and worked with Kelley to investigate amyloid beta, said that Kelley’s research findings were especially important because the research team was able to acquire intact samples of human brains from people both with and without Alzheimer’s.

Acquiring human brain tissue is a complicated and difficult process, he said; the UTSA study is one of only two research initiatives in the U.S. in which imaging mass spectrometry on human tissue has been used to research the makeup of plaques that contribute to Alzheimer’s disease. The vast majority of Alzheimer’s studies use mice, limiting researchers to inducing and then removing beta amyloids that do not occur naturally in the species, he said.

“It has been shown that mice show little pathological resemblance to humans when it comes to brain chemistry,” Bach said.

Kelley needed nine months to master the technique used to extract amyloid beta plaque from fixed human brain tissue to complete imaging mass spectrometry.

“[The procedure] is very challenging, and their success in this regard is exciting,” said Dr. Sudha Seshadri, direct of UT Health San Antonio’s Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “It could increase the number of samples available, as well as the precision at which you can study the chemistry of the plaque.”

Seshadri said that when it comes to Alzheimer’s research, “all new approaches are welcome” as scientists and medical professionals work to get a grasp on a disease that yields a newly diagnosed case every 66 seconds.

“The fact that we can look at this tissue and use new techniques to identify protein in the plaque” could result in newer treatments, Seshadri said.

Roseanna Garza

Roseanna Garza

Roseanna Garza reports on health and bioscience for the San Antonio Report.