An Alzheimer’s treatment study completed by UC Irvine researchers after two-and-a-half-years concluded that beta-amyloid peptide, a type of brain pathology that appears in plaques found in patients with Alzheimer’s disease, can be significantly reduced in canines by immunotherapy, and was published in the April 2 issue of the Journal of Neuroscience. However, researchers also found that the reduction of brain plaque does not immediately improve memory or learning behavior, but long-term treatment leads to protection of neurological functions.
The study was conducted by UCI’s Institute for Brain Aging and Dementia, the Department of Neurology and the Department of Molecular Biology and Biochemistry, in conjunction with research colleagues at Lovelace Respiratory Research Institute in Albuquerque, New Mexico.
In the study, nine out of 20 beagles received monthly vaccinations with an ingredient that included beta-amyloid 1-42, a key peptide that plays a role in memory and learning loss in the brains of Alzheimer’s patients. The other 11 canines were used as the control group.
During the experiment, it was still difficult for the treated beagles to remember the new location of their meals. However, the very last few months of the study showed that after years of vaccinations, the treated beagles did indeed become quicker with decision-making. Later, necropsies showed a small amount of beta-amyloid left in the beagles’ brains.
Dr. Elizabeth Head, a UCI neurobiologist and researcher who oversaw the project, believes this is a building block to find an effective treatment for Alzheimer’s.
“Now we know that the vaccine is very effective, so we can move forward with researching other ways to treat patients,” Head said. According to Head, results from this research are significant advancements in the study of Alzheimer’s treatment because researchers can now tackle their next step: finding a way to repair salvageable neurons that were exposed to plaques. Head believes that the mending of neurons, in addition to forms of mental and physical exercise, or “environmental enrichment,” such as crossword puzzles and jogging, may be able to improve the state of an Alzheimer’s patient.
Although Head is hopeful for future advancements regarding treatment, she said that it is currently difficult to detect and reduce Alzheimer’s before irrevocable neuron destruction. “If we caught someone early in the disease, we could stop it from getting worse. But by the time most Alzheimer’s patients complain of memory problems, there may already be extensive neuron damage and plaques,” Head said.
Because canines were used, this study is one of the first of its kind. Viorela Pop, a graduate student researcher, said that beagles naturally create brain plaque in old age, as do humans, which was a considerable advantage to this study. “I believe it is important to test Alzheimer therapies in a higher animal models such as the beagle. However, there are benefits to using mice, too. They have a shorter lifespan and allow researchers to ask questions and perform studies that may not be possible in dogs,” Pop said.
Pop also helped with biochemical analyses on post-mortem canine brain tissue and examined various types of beta-amyloid species to determine the kinds of beta-amyloid that decreased. In preparation for analysis, each brain was split into the left and right hemispheres. Of each brain, one half was frozen while the other half was fixed in a solution and kept at a cool four degrees Celsius, about the temperature of a basic refrigerator. Then, the fixed solution hemisphere was sectioned into slices 40 microns thin, which is roughly the width of six strands of a spider’s web. When the tissue returned to UCI, Pop aided in immunostaining the delicate slices, which, in turn, highlighted the beta-amyloid proteins.
The researchers studied four brain regions, and the greatest amount of plaque reduction was found in the prefrontal cortex, which is responsible for functions like planning and decision-making.
“We found reductions in beta-amyloid that accumulate in extracellular plaques, and specifically in two major beta-amyloid species,” Pop explained. “Both [beta-amyloids] in the brain were drastically reduced because of the vaccine.”