Molecular markers of early Parkinson's disease based on gene expression in blood.
Parkinson's disease (PD) progresses relentlessly and affects five million people worldwide. Laboratory tests for PD are critically needed for developing treatments designed to slow or prevent progression of the disease. We performed a transcriptome-wide scan in 105 individuals to interrogate the molecular processes perturbed in cellular blood of patients with early-stage PD. The molecular multigene marker here identified is associated with risk of PD in 66 samples of the training set comprising healthy and disease controls [third tertile cross-validated odds ratio of 5.7 (P for trend 0.005)]. It is further validated in 39 independent test samples [third tertile odds ratio of 5.1 (P for trend 0.04)]. Insights into disease-linked processes detectable in peripheral blood are offered by 22 unique genes differentially expressed in patients with PD versus healthy individuals. These include the co-chaperone ST13, which stabilizes heat-shock protein 70, a modifier of alpha-synuclein misfolding and toxicity. ST13 messenger RNA copies are lower in patients with PD (mean +/- SE 0.59 +/- 0.05) than in controls (0.96 +/- 0.09) (P = 0.002) in two independent populations. Thus, gene expression signals measured in blood can facilitate the development of biomarkers for PD.
Scherzer
Clemens R
CR
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA. cscherzer@rics.bwh.harvard.edu
Eklund
Aron C
AC
Morse
Lee J
LJ
Liao
Zhixiang
Z
Locascio
Joseph J
JJ
Fefer
Daniel
D
Schwarzschild
Michael A
MA
Schlossmacher
Michael G
MG
Hauser
Michael A
MA
Vance
Jeffery M
JM
Sudarsky
Lewis R
LR
Standaert
David G
DG
Growdon
John H
JH
Jensen
Roderick V
RV
Gullans
Steven R
SR
D015415:Biomarkers / Q000097:blood; D015870:Gene Expression; D020869:Gene Expression Profiling; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D010300:Parkinson Disease / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D012307:Risk Factors; D013997:Time Factors
D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins