Neuronal gene expression correlates of Parkinson's disease with dementia.
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.
Stamper
Chelsea
C
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.
Siegel
Andrew
A
Liang
Winnie S
WS
Pearson
John V
JV
Stephan
Dietrich A
DA
Shill
Holly
H
Connor
Don
D
Caviness
John N
JN
Sabbagh
Marwan
M
Beach
Thomas G
TG
Adler
Charles H
CH
Dunckley
Travis
T
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
D009419:Nerve Tissue Proteins