title: Neuronal gene expression correlates of Parkinson's disease with dementia.
abstract: Dementia is a common disabling complication in patients with Parkinson's disease (PD). The underlying molecular causes of Parkinson's disease with dementia (PDD) are poorly understood. To identify candidate genes and molecular pathways involved in PDD, we have performed whole genome expression profiling of susceptible cortical neuronal populations. Results show significant differences in expression of 162 genes (P < 0.01) between PD patients who are cognitively normal (PD-CogNL) and controls. In contrast, there were 556 genes (P < 0.01) significantly altered in PDD compared to either healthy controls or to PD-CogNL cases. These results are consistent with increased cortical pathology in PDD relative to PD-CogNL and identify underlying molecular changes associated with the increased pathology of PDD. Lastly, we have identified expression differences in 69 genes in PD cortical neurons that occur before the onset of dementia and that are exacerbated upon the development of dementia, suggesting that they may be relevant presymptomatic contributors to the onset of dementia in PD. These results provide new insights into the cortical molecular changes associated with PDD and provide a highly useful reference database for researchers interested in PDD.
authors.affiliation: Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Stamper
authors.forename: Andrew
authors.initials: A
authors.lastname: Siegel
authors.forename: Winnie S
authors.initials: WS
authors.lastname: Liang
authors.forename: John V
authors.initials: JV
authors.lastname: Pearson
authors.forename: Dietrich A
authors.initials: DA
authors.lastname: Stephan
authors.forename: Holly
authors.initials: H
authors.lastname: Shill
authors.forename: Don
authors.initials: D
authors.lastname: Connor
authors.forename: John N
authors.initials: JN
authors.lastname: Caviness
authors.forename: Marwan
authors.initials: M
authors.lastname: Sabbagh
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.forename: Charles H
authors.initials: CH
authors.lastname: Adler
authors.forename: Travis
authors.initials: T
authors.lastname: Dunckley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003704:Dementia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology
chemical_list: D009419:Nerve Tissue Proteins