Summary: Glatiramer acetate, a drug commonly prescribed for the treatment of multiple sclerosis, improved memory in mouse models of Alzheimer’s disease.
Source: University of Rochester
Losing memory is a hallmark of Alzheimer’s, a symptom of the disease that depletes a patient’s quality of life. Improving memory and slowing cognitive changes caused by the disease is an ongoing challenge for researchers seeking to develop novel therapies.
In a newly published paper in Frontiers in Neuroscience, researchers at the Del Monte Institute for Neuroscience at the University of Rochester found that glatiramer acetate, a prescription drug currently used to treat patients with multiple sclerosis (MS), improved memory in a mouse model of Alzheimer’s disease.
“This research extends our information about glatiramer acetate’s potential use in Alzheimer’s disease,” said M. Kerry O’Banion, M.D., Ph.D., professor of Neuroscience and senior author of the study. “This isn’t a cure, but it could be a step in the right direction for a treatment to slow the symptoms of this debilitating disease.”
Using a mouse model, researchers found changes in microglia—part of the brain’s immune system—and improvements in cognitive behavior when glatiramer acetate was used. These changes were associated with less amyloid plaques and modifications to tau pathology—a protein found in neurodegenerative diseases—in the brain, indicating that molecular hallmarks of Alzheimer’s disease had been impacted.
Previous studies have found that glatiramer acetate can alter brain pathology in Alzheimer’s disease mouse models, but the exact mechanisms that are impacted in the brain are still unknown.
“Overall, these findings provide further evidence that therapies that modify the immune system could be effective in the treatment of Alzheimer’s disease,” said Dawling Dionisio-Santos, Ph.D., a first-year resident in Neurology and graduate of the Medical Scientist Training Program and co-first author on the paper. “It adds evidence to support trials that test the use of glatiramer acetate in patients at risk for developing Alzheimer’s.”
Co-authors on this paper include Berke Karaahmet, Elizabeth K. Belcher, Ph.D., Laura D. Owlett, Ph.D., Lee A. Trojanczyk, and John A. Olschowka, Ph.D. The research was funded by the National Institute on Aging.
Neuroinflammation driven by the accumulation of amyloid β (Aβ) can lead to neurofibrillary tangle formation in Alzheimer’s Disease (AD).
To test the hypothesis that an anti-inflammatory immunomodulatory agent might have beneficial effects on amyloid and tau pathology, as well as microglial phenotype, we evaluated glatiramer acetate (GA), a multiple sclerosis drug thought to bias type 2 helper T (Th2) cell responses and alternatively activate myeloid cells.
We administered weekly subcutaneous injections of GA or PBS to 15-month-old 3xTg AD mice, which develop both amyloid and tau pathology, for a period of 8 weeks. We found that subcutaneous administration of GA improved behavioral performance in novel object recognition and decreased Aβ plaque in the 3xTg AD mice.
Changes in tau phosphorylation were mixed with specific changes in phosphoepitopes seen in immunohistochemistry but not observed in western blot. In addition, we found that there was a trend toward increased microglia complexity in 3xTg mice treated with GA, suggesting a shift toward homeostasis.
These findings correlated with subtle changes in the microglial transcriptome, in which the most striking difference was the upregulation of Dcstamp. Lastly, we found no evidence of changes in proportions of major helper T cell (Th) subtypes in the periphery.
Overall, our study provides further evidence for the benefits of immunomodulatory therapies that alter the adaptive immune system with the goal of modifying microglia responses for the treatment of Alzheimer’s Disease.