Cyrus P. Zabetian
Dept.: Associate Professor, Department of Neurology; Division of Neurogenetics; Staff Neurologist, VA Puget Sound Health Care System
Neuroscience Focus Groups:
My laboratory studies the genetics of neurodegenerative diseases, particularly Lewy body disorders which include Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Current projects include the discovery of novel susceptibility and modifier genes for PD/DLB, and the clinical and neuropathological characterization of monogenic forms of these disorders.
Our work in identifying novel risk genes involves genome-wide analysis of both large case-control samples and multiplex families through worldwide collaborations. We are also taking into consideration potential interaction with environmental factors such as caffeine and nicotine exposure.
In addition to susceptibility genes, we are seeking to discover genes that modify phenotype. For example, cognitive impairment frequently develops after onset of motor symptoms in PD. We hope to find genes that predict the rate of cognitive decline and conversion to dementia in PD through longitudinal assessment of PD cohorts at several centers across the U.S.
Several genes underlying monogenic forms of PD have been discovered over the past decade, including PARK2 and LRRK2. Also, variation in the GBA gene have been shown to convey a 5-6 fold increase in risk for Lewy body disorders. We are studying the clinical characteristics of patients who carry mutations in these genes, and also how mutation spectrum and frequency vary across the world.