Parkinson’s disease is the second-most prevalent neurodegenerative disorder after Alzheimer’s disease, with approximately two percent of the population older than 65 years being affected. Clinically, Parkinson’s disease is characterized by its predominant motor symptoms, which are the result of a profound deficiency of dopamine neurons in the basal ganglia with degeneration of the substantia nigra pars compacta. Tremor, slowness of movement, rigidity, postural instability, and a good response to levodopa therapy are displayed, and the disease is gradually progressive. In most patients, hallmark protein inclusions (Lewy bodies and Lewy neurites) are found within remaining neurons post-mortem.
The Udall Center of Excellence in Parkinson Disease Research at the Mayo Clinic is an integrated, multi-disciplinary research program that brings together neurologists, neuropsychologists, geneticists, neuropathologists, and basic scientists in the study of the “Genetics and Molecular Biology of Parkinsonism.” The Center draws upon the clinical strengths of the Mayo Clinic Movement Disorder Section and the epidemiologic and longitudinal studies of Parkinson disease, dementia with Lewy bodies, and aging and dementia for the clinical material used in the research projects, as well as strong institutional commitment to Parkinson’s disease research in the form of faculty research funds, an invited speaker seminar series, sponsorship of Movement Disorder fellowships, and pilot research grants, as well as generous support for faculty travel to promote intra-institutional collaborations. Among the major achievements that the Udall Center can claim in the previous funding cycle is discovery of the most common genetic cause of late onset autosomal dominant Parkinson’s disease—leucine-rich repeat kinase 2 (LRRK2); identification of genetic variants in the α-synuclein gene (SNCA) that are risk factors for PD; evidence that incidental Lewy body disease is pre-clinical Parkinson’s disease; validation of the neuropathologic criteria for dementia with Lewy bodies; and development of a novel synuclein construct (with leucine zipper tags) that permits rapid aggregation in vitro and in cell culture for potential drug screening.