RNA Binding Proteins in Alzheimer's Disease

Benjamin Wolozin, MD, PhD
Boston University Medical Center (Boston, MA, United States)
Year Awarded:
Grant Duration:
July 1, 2012 to June 30, 2014
Alzheimer's Disease
Award Amount:
Grant Reference ID:
Award Type:
Award Region:
US Northeastern
The grant was made possible due to a generous bequest from the Patsie Lee Clark Trust in memory of James Sterling Clark and Patsie Lee Clark.
Benjamin Wolozin, MD, PhD

RNA Binding Proteins in Alzheimer's Disease


RNA binding proteins (RBPs) regulate the conversion of messenger RNA into protein through the formation of complexes, termed RNA granules. Cellular stresses induce formation of a particular type of complex, termed the stress granules (SG). By examining SGs, the study authors have identified a new and previously unknown consequence of Alzheimer's disease. In this project they are investigating how these SGs might contribute to the causes and may provide a method of diagnosing Alzheimer's disease.


The function of RNA is to help translate the genetic “blueprint” of DNA information into actual proteins that execute the majority of functions in a cell.  RNA binding proteins (RBPs) regulate the conversion of messenger RNA to protein through formation of complexes called RNA granules. Chemical stresses induce formation of a particular type of complex termed the stress granules (SG). 

Thus, SGs present a new effect of Alzheimer's disease that is prevalent throughout the Alzheimer's disease brain.  This effect has not been studied previously, yet could be as important for understanding the causes of Alzheimer's disease as the classic investigations of the hallmark “plaques and tangles.”

The pattern of SG pathology varies depending on the RNA binding proteins being investigated. Some kinds of SGs initially do not co-localize with pathological tau, but merge with these tau deposits as the disease progresses.  In contrast, another type of SG appears as dense granules early in the disease course, but the accumulation occurs in neurons that lack similar tau markers. These data identify novel types of molecular pathology that can both correlate with tau pathology or can highlight other molecular pathologies in neurons that lack classic markers of tau pathology.  The investigators hypothesize that RNA granules, such as SGs, are present in neurons that are stressed or injured by Alzheimer's disease. Further, since these newly illuminated neurons are not able to be observed with classic markers of AD pathology, these SG markers may offer a new class of biomarkers for measuring the incidence or progression of AD.  This study is designed to probe the relationship between stress granules and pathologic tau by determining whether specific RNA binding proteins can modify the formation of tau pathology.

About the Researcher

Benjamin Wolozin, M.D., Ph.D. is a professor of Pharmacology and Neurology at Boston University School of Medicine. Wolozin's research investigates the pathophysiology of neurodegenerative diseases. His research investigates the mechanisms by which genes cause dementia (Alzheimer's disease and Frontotemporal Dementia) and movement disorders (Parkinson's disease and Amyotrophic Lateral Sclerosis). His laboratory is actively using these approaches to identify novel compounds for therapy and diagnosis of neurodegenerative diseases. Dr. Wolozin graduated magna cum laude from Wesleyan University in Middletown, CT. He earned his M.D. and Ph.D. degrees from Albert Einstein College of Medicine in New York and did his postdoctoral fellowships at the National Institute of Mental Health (1989 – 96). In addition to his BrightFocus award, Wolozin has received numerous awards for his research including the Donald B. Lindsley Prize, Society for Neuroscience, the A. E. Bennett Award from the Society for Biological Psychiatry, the Merit Award from Alzforum, the Graduate Faculty of the Year Award from Loyola University Medical Center, and the Memory Ride Award from the Massachusetts Chapter of the Alzheimer Association.
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