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Michael A. Hauser, PhD; Yi-Ju Li, PhD; Hong Xu, MA; Maher A. Noureddine, PhD; Yujun S. Shao, PhD; Steven R. Gullans, PhD; Clemens R. Scherzer, MD; Roderick V. Jensen, PhD; Adam C. McLaurin, BA; Jason R. Gibson, BA; Burton L. Scott, MD; Rita M. Jewett, RN; Judith E. Stenger, PhD; Donald E. Schmechel, MD; Christine M. Hulette, MD, PhD; Jeffery M. Vance, MD, PhD

Arch Neurol. 2005;62:917-921.

Background  Parkinson disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra. Genes contributing to rare mendelian forms of PD have been identified, but the genes involved in the more common idiopathic PD are not well understood.

Objectives  To identify genes important to PD pathogenesis using microarrays and to investigate their potential to aid in diagnosing parkinsonism.

Design  Microarray expression analysis of postmortem substantia nigra tissue.

Patients  Substantia nigra samples from 14 unrelated individuals were analyzed, including 6 with PD, 2 with progressive supranuclear palsy, 1 with frontotemporal dementia with parkinsonism, and 5 control subjects.

Main Outcome Measures  Identification of genes significantly differentially expressed (P<.05) using Affymetrix U133A microarrays.

Results  There were 142 genes that were significantly differentially expressed between PD cases and controls and 96 genes that were significantly differentially expressed between the combined progressive supranuclear palsy and frontotemporal dementia with parkinsonism cases and controls. The 12 genes common to all 3 disorders may be related to secondary effects. Hierarchical cluster analysis after exclusion of these 12 genes differentiated 4 of the 6 PD cases from progressive supranuclear palsy and frontotemporal dementia with parkinsonism.

Conclusions  Four main molecular pathways are altered in PD substantia nigra: chaperones, ubiquitination, vesicle trafficking, and nuclear-encoded mitochondrial genes. These results correlate well with expression analyses performed in several PD animal models. Expression analyses have promising potential to aid in postmortem diagnostic evaluation of parkinsonism.

Author Affiliations: Center for Human Genetics (Drs Hauser, Li, Noureddine, Shao, Stenger, and Vance, Messrs Xu, McLaurin, and Gibson, and Ms Jewett), Morris K. Udall Parkinson Disease Research Center of Excellence (Drs Hauser, Li, Noureddine, Scott, Hulette, and Vance, Messrs Xu, McLaurin, and Gibson, and Ms Jewett), and Departments of Pathology (Dr Hulette) and Medicine (Drs Hauser, Li, Schmechel, and Vance), Duke University, Durham, NC; Center for Neurologic Diseases and Morris K. Udall Parkinson Disease Research Center of Excellence, Harvard Medical School, Brigham and Women’s Hospital, Cambridge, Mass (Drs Gullans, Scherzer, and Jensen); and Department of Physics, Wesleyan University, Middletown, Conn (Dr Jensen).

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