The Brain Institute has created a new, expanded brain bank to give researchers across the country a chance to study human brain tissue that has been damaged by neurodegenerative disease. Supported with a grant from the Henry L. Hillman Foundation Opportunity Fund, the Brain Institute Brain Bank collects tissue that has been altered by a wide variety of diseases, including Alzheimer’s and other forms of dementia, Parkinson’s, amyotrophic lateral sclerosis (ALS), traumatic brain injury, chronic traumatic encephalopathy, and pediatric neurodegenerative disorders.
Why is this important? Most studies of these diseases use animal models -- typically, mice and rats. These studies are useful but limited. “Animals don’t live long enough to get any of the human neurodegenerative diseases,” says Clayton A. Wiley, MD, PhD, PERF Endowed Professor of Pathology and Director of the Division of Neuropathology. “So although a lot of important work has come out of animal studies, we need human tissue in order to fully understand the pathology of these devastating illnesses.”
Researchers can use the brain bank to test and translate their findings in tissue that displays the full characteristics of actual human diseases. In addition, banking tissue of many different disorders will enable discovery of ways in which some brain diseases overlap, as well as how they are critically different.
“Common mechanisms are likely to be key to discovering new diagnostic tools and treatments,” says Nathan Urban, PhD, Associate Director of the Brain Institute and Co-Director of the Center for the Neural Basis of Cognition, a joint program of Pitt and Carnegie Mellon University. Analysis of the neuropathology of neurodegenerative diseases will allow researchers to identify common pathways linking genes, brain injury, neurodegeneration and disease processes. “We want to provide access to a broad group of researchers studying a number of different diseases at the University of Pittsburgh and beyond. This new brain bank is a way to do that.”
The bank is directed by Julia Kofler, MD, Assistant Professor of Pathology.
(Read about five additional neuroscience projects at Pitt that the Henry L. Hillman Foundation supports.)
How is this brain bank different from others? First, the original bank had its start 30 years ago, and already contains more than 1,000 brains that are fully characterized. That means that neuropathologists have used all the gold-standard assessment tools to note variations seen in diseased and normal brains. Use of this information can be expected to speed translation of animal findings to potential treatments and cures in people. Second, many banks specialize in a particular disease, such as multiple sclerosis, rather than the broad range of diseases cataloged in the Brain Institute Brain Bank. Notably, the bank already has one of the nation’s largest brain collections related to ALS and Alzheimer’s disease.
What does the brain bank offer to scientists? Investigators have free access to specific tissue relevant to their research, and to full descriptions and annotations by neuropathologists of what veers from normal in these brains. Perhaps most important, Brain Institute experts in neuropathology can collaborate with scientists to help them make connections with their work in rodent models. For instance, investigators might choose to use RNA sequencing or mass spectroscopy to analyze human tissue, and then refine their hypotheses about the disorder in question. Such honing, in turn, can lead to better testing, both in animal models and diseased human tissue. Recently, Kofler and Wiley assisted investigators in the Pittsburgh Institute for Neurodegenerative Diseases, who were able to confirm that a molecular marker of Parkinson’s disease in mice was also present in human tissues. In another ongoing research effort, Kofler and Chris Donnelly, PhD, assistant professor of neurobiology, are exploring the similarities of a pluripotent human stem-cell model of ALS with post-mortem brain tissue of patients who had the disease.