CORE--GENETICS

University Of California, San Diego, La Jolla CA

Investigators

Linked publications & trials

Abstract

Multiple system atrophy (MSA) is a progressive neurodegenerative disease of unknown etiology. It is characterized by varying combinations of parkinsonian, cerebellar, autonomic and pyramidal features. Despite these varying clinical features, in all cases of MSA there is a common finding of glial cytoplasmic inclusions (GCIs) in the brains of patients at autopsy. Similar to the Lewy body inclusions found in brains of Parkinson's disease patients, the major component of GCIs is alpha-synuclein. Like the majority of PD cases, MSA appears to be a sporadic disorder however, only a single systematic study has been undertaken to assess familial aggregation. This investigation did not find other relatives with MSA but did note a higher proportion of relatives with parkinsonism and symptoms such as trouble swallowing, speech changes and unsteadiness. While the sporadic occurrence of MSA suggests that environmental factors play a substantial role in the development of MSA, it is possible that an underlying genetic predisposition may be important as well. Similarly, in progressive supranuclear palsy (PSP), a disease characterized by sporadic occurrence of parkinsonism with tau tangle pathology, several studies have confirmed an association between a haplotype in the 5' end of the tau gene and individuals with sporadic PSP. The main goals of this Core are 1) to isolate and store DNA from 165 MSA patients and 330 controls enrolled in the Program Project 2) extract DNA from confirmed MSA brain samples 3) genotype a limited number of candidate genes associated to augment pathological characterization by Core C and identify potential susceptibility loci that may predispose an individual to MSA.