Many brain disorders are nearly impossible to diagnose until symptoms become apparent, making early intervention a challenge. But groundbreaking research funded by the National Institutes of Health and led by Michael I. Miller, director of the Johns Hopkins Department of Biomedical Engineering, is ushering in a new era for diagnosing and treating these debilitating conditions years before symptoms surface.
Throughout his trailblazing career, Miller has transformed our understanding of neurological diseases that impact millions of Americans and their families, including Alzheimer's, Huntington's, dementia, schizophrenia, and epilepsy.
Miller's current work focuses on early diagnostic and therapeutic approaches (theranostics) using computational methods to link precise diagnostic techniques with targeted therapies in the temporal lobe regions of the brain involved in Alzheimer's disease. Researchers in his lab use an enhanced form of magnetic resonance imaging (MRI) and molecular markers to map how the brain's structure and function change over the course of disease progression. They look at how these changes relate to known hallmarks of Alzheimer's disease, such as amyloid plaques and Tau tangles in the brain.
To conduct his work, Miller uses real patient data from the NIH-funded BIOCARD project, one of the largest Alzheimer's studies in the world led by Marilyn Albert, a professor of neurology at Johns Hopkins School of Medicine. More recently, and in collaboration with Meaghan Morris, a Johns Hopkins assistant professor of pathology and neuropathology, Miller is using such patient data to investigate changes in gene expression associated with Alzheimer's. Their discoveries are setting the stage for early detection, disease monitoring, and personalized treatment.
"We are finding more and more evidence that Alzheimer's is possible to detect early, during a window when treatments may be more effective," Miller says. "We believe that such insights will guide the development of preventive treatments that target these subtle brain changes rather than merely addressing the symptoms."
Miller's work contributed to shaping the NIH's 2011 diagnostic criteria for Alzheimer's disease and demonstrated MRI's potential as a powerful and noninvasive tool for early detection. In a landmark 2014 NIH study, Miller and collaborators were the first to prove that MRI scans can detect changes in the brain—specifically in the medial temporal lobe—that are linked to Alzheimer's. They showed that these changes can be seen more than 10 years before people start showing symptoms.
This early detection capability is critical because with the American population aging, the number of people afflicted by the disease could reach 14 million by 2050, according to the Alzheimer's Association. While clinicians currently lack the means to prevent or even slow down the disease, early detection still offers benefits, from allowing patients and their families to plan for the future, enabling lifestyle modifications that can improve quality of life, and providing opportunities to participate in clinical trials.
"But thanks to decades of rigorous research and critical funding support from the NIH," Miller says, "early interventions and treatments that work better than anything currently available are now within reach."
To transform this potential into reality, another pillar of Miller's research group is bringing scientists and data together to make progress not possible before. His group has built MRICloud, a brain image database widely available to the scientific community so others can pursue imaging-based research on brain disease.
Miller says that the most important biomedical discoveries hinge on teamwork, from the clinicians who treat patients to the biomedical scientists doing fundamental research that provides the groundwork for future treatments and cures.
"Science advances when a community of forward-thinking researchers, such as we have here at Hopkins, work closely together to pursue solutions that help real people," he says.
