title: Expression profiling of substantia nigra in Parkinson disease, progressive supranuclear palsy, and frontotemporal dementia with parkinsonism.
abstract: 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.
  
  
  OBJECTIVE
  To identify genes important to PD pathogenesis using microarrays and to investigate their potential to aid in diagnosing parkinsonism.
  
  
  METHODS
  Microarray expression analysis of postmortem substantia nigra tissue.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA. mike.hauser@duke.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Maher A
authors.initials: MA
authors.lastname: Noureddine
authors.forename: Yujun S
authors.initials: YS
authors.lastname: Shao
authors.forename: Steven R
authors.initials: SR
authors.lastname: Gullans
authors.forename: Clemens R
authors.initials: CR
authors.lastname: Scherzer
authors.forename: Roderick V
authors.initials: RV
authors.lastname: Jensen
authors.forename: Adam C
authors.initials: AC
authors.lastname: McLaurin
authors.forename: Jason R
authors.initials: JR
authors.lastname: Gibson
authors.forename: Burton L
authors.initials: BL
authors.lastname: Scott
authors.forename: Rita M
authors.initials: RM
authors.lastname: Jewett
authors.forename: Judith E
authors.initials: JE
authors.lastname: Stenger
authors.forename: Donald E
authors.initials: DE
authors.lastname: Schmechel
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hulette
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Vance
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D003704:Dementia / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology*; D013494:Supranuclear Palsy, Progressive / Q000235:genetics* / Q000473:pathology