Common GBA Variants in Parkinson’s Disease and Lewy Body Dementia Patients

PROJECT OF MERIT

Research Authorship:

Megan T. Mazak, Ronald L. Walton, BSc, Alexandra I. Soto, MS, Zbidniew K. Wszolek, MD, Dennis W. Dickson, MD, Owen A. Ross, Ph.D.

Faculty Mentor:

Dr. Judith D. Ochrietor   |   College of Arts and Sciences   |   Department of Biology
Ronald L. Wilson, MMS  |   Mayo Foundation for Medical Education and Research   |   Department of Neuroscience

Abstract:

Parkinson’s disease (PD) and Lewy Body Dementias (LBD) are two distinct synucleinopathies with a great amount of symptomatic and genetic overlap. This overlap can often lead to misdiagnosis. Misdiagnosis can result in improper therapy and therefore a poorer prognosis. LBD is a neuropath diagnosis with subcategories, but for the purpose of this project we discuss LBD as a whole. GBA is a gene common to both diseases with different effect sizes in each, although increasing severity of disease for both. Common is defined as a presence greater than 1% in healthy controls. GBA is found in 2-37% of Parkinson cases worldwide, with Ashkenazi Jews having the highest frequency of mutation. Our PD cohort is a clinical series, whereas our LBD cohort is a pathological series. A clinical LBD series can skew results as they are often misdiagnosed, so there is more certainty behind a pathological series. Here, we screened ~200 samples for E365K and T408M, two common GBA variants. We have reviewed the clinical implications of being a GBA carrier for both diseases and have identified differences. We have genotyped ~1200 LBD samples for these two common variants. Now that we know GBA plays a role in each disease, we can better understand the mechanism of pathogenesis and can identify potential therapy targets for GBA carriers. These therapeutic targets could be a gateway to cures and therapies for an otherwise incurable condition.