Since completion of her Ph.D. in 2016, Assistant Professor Melissa Edler and her colleagues have secured more than $2 million in research funding for examining aging and neurodegenerative diseases. Eventually, this research could help millions of people find a better way to combat and live with harsh brain diseases.
Edler began examining the brains of aged chimpanzees for Alzheimer’s disease (AD) pathology as part of her dissertation at Kent State University. AD is characterized by the buildup of two toxic proteins, amyloid-beta (Aβ) which forms plaques and tau which is associated with neurofibrillary tangles (NFT). At the time, several species had been found to develop Aβ plaques or NFT, but only one animal exhibited both pathologies — a chimpanzee. Initially, Edler and her colleagues, who were not part of the original study, did not think the pathology was related to AD.
“We thought it was a bit of a fluke, because this animal had a stroke,” Edler said. “Pretty quickly, we realized that we were wrong and that chimpanzees naturally develop both Aβ plaques and NFT.”
However, it was impossible to accurately assess whether the animal had suffered from the same dementia symptoms as humans such as memory loss and deficits in executive and motor function.
Exploring this phenomenon became the center of Edler’s research today. Edler and her colleagues, including her mentor and Ph.D. advisor Mary Ann Raghanti, chair of the anthropology department, were awarded over $1.2 million by the National Institutes of Health (NIH) in 2021 to examine pathology, genetic and behavioral changes associated with AD pathology in chimpanzees. One of the primary goals of the grant is to establish whether AD pathology in chimpanzees is associated with cognitive impairment.
“By analyzing similarities and differences between species, we hope to figure out whether the human brain is uniquely vulnerable or if the chimpanzee brain is protected from developing AD,” Edler said. “For example, chimpanzees have significant Aβ deposition, but they have very few NFT, minimal cell loss and mild cognitive impairment compared to humans with AD. Therefore, determining why chimpanzees do not develop significant numbers of NFT despite having high Aβ levels could be a key component in understanding the pathophysiology of the disease and lead us to new areas of focus for clinical treatments by other groups.”
This comparative approach could bring seminal results, but it is only one part of a larger project. In January, the National Institute on Aging, part of the NIH, awarded more than $600,000 to Edler and her collaborator, William Hopkins, director of the Keeling Center for Comparative Medicine and Research at the University of Texas MD Anderson Cancer Center, to expand this research.
“Most of the current treatments for AD [for humans] target neurotransmitters like acetylcholine, which is lost in certain brain regions as the disease progresses. However, these treatments only help reduce symptoms for a short period of time, and they do not target the neurological basis of the disease,” Edler said.
In the new grant, Edler and Hopkins will investigate whether geriatric chimpanzees with AD pathology experience the same neurotransmitter loss or motor impairments as humans with AD or Parkinson’s disease (PD). Through both grants, Edler and her colleagues have access to nearly 80 chimpanzee samples from the NIH-funded National Chimpanzee Brain Resource (NCBR), housed at The George Washington University and from the Great APE Aging Project, as well as human samples from the NIH NeuroBioBank.
In addition, Edler was part of another NIH grant that investigated how long-term manganese exposure relates to PD-like symptoms.
Manganese is an element found naturally in the body, but long-term exposure, such as working in the steel industry, mining or even using certain hard drugs, can cause what's called manganese neurotoxicity.
“High levels of manganese in the brain can cause Parkinson's disease-like symptoms, such as muscle rigidity, gait instability and cognitive deficits,” Edler said. “In the past, patients with manganese toxicity were treated with L-dopa, which is used for replacing dopamine levels in the brains of PD patients, but it didn’t work in these individuals.”
Led by collaborator Tomás Guilarte, dean and professor of environmental health sciences at Florida International University, Edler is helping to analyze other possible neurotransmitter pathways that may be involved, which could lead to future therapeutic options.
Though Edler is proud of her catalog, she credits her success to her close-knit team at Kent State and beyond. “A lot of our success has to do with our collaborative network of neuroscientists, anthropologists, primatologists, geneticists and biologists that we work with regularly,” Edler said. “In addition, we have great research facilities at Kent State to do the work as well as the support of Research and Sponsored Programs and the Brain Health Research Institute.”
As she continues her research, Edler will be representing Kent State and showing that it is at the forefront of groundbreaking research.
To learn more about Edler’s research projects, please visit her publication catalog.
To learn more about Research and Sponsored Programs, please visit their webpage.