Department of Neurology
Washington University School of Medicine
Dr. Ghoshal is currently an Assistant Professor in Neurology at Washington University. She obtained her M.D., Ph.D. from Northwestern University and her graduate work focused on conformational changes in tau protein that occur during the progression of Alzheimer’s disease. She did her clinical training in neurology at Washington University in St. Louis and did postdoctoral research with Dr. Alison Goate and Dr. Nigel Cairns where she characterized progranulin knockout mice as a model for frontotemporal dementia. Her current research project focuses on identifying novel biomarkers in presymptomatic individuals with frontotemporal dementia.
BIRCWH Scholar from 01/01/2012 until 12/31/2014
Clinical and Biomarker Characterization of Inherited Frontotemporal Dementia
Frontotemporal dementia (FTD) is an increasingly recognized cause of dementia, particularly in individuals <70. There are three subtypes of FTD including behavioral variant FTD (bvFTD), semantic dementia (SD), and progressive non-fluent aphasia (PNFA). Of these, PNFA affects women 2-to-1 over men 23,24. For bvFTD and SD, men are affected 2-to-1 over women, leaving women to be the long-term caregivers for these early onset dementias 23-25. Furthermore, FTD is a condition for which there is no currently effective symptomatic or disease modifying therapy. Like Alzheimer’s disease (AD)21,22,26-32, the most successful treatment approach for FTD may be prevention of its symptomatic stage. This in turn suggests that there is a preclinical stage of FTD, when brain changes are already established but have not yet culminated in symptomatic disease. Although Washington University (WU), through its Knight Alzheimer Disease Research Center (KADRC), has an internationally established program in preclinical AD, there is no equivalent program for preclinical FTD despite available participant, clinical, and translational resources. I propose to use these resources to identify for the first time preclinical FTD by developing FTD-related behavioral and biofluid biomarkers. I predict that these biomarkers will improve the diagnostic accuracy of FTD, reveal the pathologic cascade culminating in symptomatic disease, identify novel therapeutic targets, and provide important intermediate outcome measures for clinical trials. I will begin these studies in families with autosomal dominantly inherited FTD caused by known mutations in tau (MAPT) or progranulin (GRN) genes. Although some members of these families already are enrolled at the Knight ADRC, there have been no efforts to develop a well-organized clinical cohort and no analyses for preclinical biomarkers have been attempted. I am ideally suited to pursue this project given my graduate training in tau biochemistry/pathology, clinical training in cognitive neurology and dementia, fellowship training in progranulin biochemistry/pathology, and my more recent involvement with FTD families enrolled at the KADRC. Because the clinical and pathological phenotypes of dominantly inherited FTD mirror the more common sporadic FTD, the sequence of brain changes in autosomal dominant FTD also may inform about underlying disease mechanisms in sporadic FTD. To our knowledge, a systematic study of FTD using biomarkers to establish a preclinical stage has not been accomplished.