INDIANAPOLIS - Indiana University is leading the way nationally as the home to one of only two centers in the United States dedicated to developing stem-cell-based models of the human brain to better understand the underlying causes of Alzheimer's disease and related dementias.
IU School of Medicine professor Jason Meyer, seen here with assistant research professor Cátia Gomes, is co-leading a new IU center focused on modeling the human brain to improve scientific understanding of Alzheimer's disease, which could lead to better treatment options for the more than 7 million Americans living with the devastating disease. Photo by Tim Yates, IU School of Medicine
Researchers from the IU School of Medicine and the IU Luddy School of Informatics, Computing and Engineering are co-leading the newly funded Microphysiological Systems to Advance Precision Medicine for Alzheimer's Disease and Related Dementias, known as MAP-AD. The center draws upon the scientific expertise in the School of Medicine's comprehensive Alzheimer's disease research program.
The center will develop brain organoids - three-dimensional cellular models derived from human pluripotent stem cells that can be developed into any type of cell in the body - to study various characteristics of Alzheimer's disease and related dementias, such as neuroinflammation and vascular dysfunction. Researchers will also lead preclinical and pharmacological studies to accelerate drug discovery and development.
"This center speaks to exciting areas of scientific investigation in the research community that is developing microphysiological systems to better understand human disease," said Jason Meyer, the A. Donald Merritt Professor of Medical and Molecular Genetics at the IU School of Medicine. "MAP-AD is a testament to the team and infrastructure that have been built up at the IU School of Medicine to support Alzheimer's disease and neurodegeneration research."
The National Institute on Aging, part of the National Institutes of Health, awarded IU a five-year, $16.5 million grant to fund MAP-AD, which is one of two centers of its kind that received NIH funding to launch such programs.
Meyer co-leads the grant with the IU School of Medicine's Scott Canfield, associate professor of anatomy, cell biology and physiology; Jeff Dage, senior research professor of neurology; Kun Huang, chair of the Department of Biostatistics and Health Data Science; Bruce Lamb, executive director of the Stark Neurosciences Research Institute; Timothy Richardson, research professor of medicine; and Donna Wilcock, the Barbara and Larry Sharpf Professor of Alzheimer's Disease Research; as well as Feng Guo, associate professor of intelligent systems engineering in the Luddy School at IU Bloomington.
More than 7 million Americans are living with Alzheimer's disease, according to the Alzheimer's Association. By 2050, this is projected to increase to nearly 13 million.
For years, many potential treatments that showed promise in the laboratory using animal models failed in clinical trials. Brain organoids better represent the complexities of the human brain and how disease progresses in humans than many animal models, Meyer said.
"There's a strong potential that we'll identify new, exciting areas of investigation using stem cell models that focus more on human-specific cellular changes in Alzheimer's disease," Meyer said. "I think this has a potential to be very impactful for the Alzheimer's research community."
Kiersten Peña, an IU School of Medicine medical neuroscience graduate student, works in Jason Meyer's lab, which develops stem-cell-based models of neurodegenerative disorders, like Alzheimer's disease. Photo by Tim Yates, IU School of Medicine
The center consists of multiple cores led by IU experts. The Administrative and Data Management Core is led by Meyer, Lamb and Wilcock; the Bioinformatics and Computational Core is led by Huang; the Microphysiological Systems Model Development and Validation Core is led by Meyer, Canfield and Guo; and the Preclinical Efficacy and Safety Core is led by Richardson and Dage.
Meyer's laboratory will focus on developing brain organoid models to better understand genetic risk variants related to neuroinflammatory aspects associated with Alzheimer's disease, including two variants in the phospholipase C gamma 2 gene. Known as PLCG2, this immune-cell-specific gene is closely associated with Alzheimer's disease and neuroinflammation.
IU School of Medicine researchers identified the PLCG2 gene mutation, and the gene is also part of a portfolio of drug targets developed by the school's Alzheimer's disease drug discovery program.
Meyer's laboratory will soon operate inside the research tower of the IU School of Medicine's new Medical Education and Research Building. Two floors of the tower will house labs dedicated to neurodegeneration research, including Alzheimer's disease, Parkinson's disease and ALS.
Canfield, a faculty member at the IU School of Medicine-Terre Haute campus, and his team of researchers will investigate cerebrovascular dysfunction in Alzheimer's disease. They'll develop cellular models to better understand the blood-brain barrier's role in the disease's progression.
Guo's laboratory at Luddy has developed pioneering organoid computing technology. The lab aims to harness artificial intelligence and intelligent systems to enable functional phenotyping of Alzheimer's disease pathology and neuroinflammation within the MAP-AD models. The ultimate goal is to advance the understanding of disease progression and accelerate therapeutic discovery.
"The convergence of organoids, artificial intelligence and medicine holds immense promise for recapitulating the pathological features and treatment responses of individual Alzheimer's disease patients," Guo said.
Richardson and Dage will leverage their expertise in drug discovery and biomarker research to translate the models for preclinical testing and pharmacological studies. The MAP-AD center will also partner with the Indiana Biosciences Research Institute to lead drug discovery research.
Through Huang's guidance in developing the bioinformatics data analysis pipeline for the cellular models, the MAP-AD center will work with Sage Bionetworks to share the new models and data sets to the research community through the AD Knowledge Portal.
Wilcock, the director of the Center for Neurodegenerative Disorders in the IU School of Medicine-IU Health Neuroscience Center, said MAP-AD is a critical piece of the school's Alzheimer's disease research program and bolsters its translational dementia research.
