Dataset Information

A monocyte gene expression signature in the early clinical course of Parkinson's disease.

ABSTRACT: Microglia are the main immune cells of the brain and express a large genetic pattern of genes linked to Parkinson's disease risk alleles. Monocytes like microglia are myeloid-lineage cells, raising the questions of the extent to which they share gene expression with microglia and whether they are already altered early in the clinical course of the disease. To decipher a monocytic gene expression signature in Parkinson's disease, we performed RNA-seq and applied the two-sample Kolmogorov-Smirnov test to identify differentially expressed genes between controls and patients with Parkinson's disease and changes in gene expression variability and dysregulation. The gene expression profiles of normal human monocytes and microglia showed a plethora of differentially expressed genes. Additionally, we identified a distinct gene expression pattern of monocytes isolated from Parkinson's disease patients at an early disease stage compared to controls using the Kolmogorov-Smirnov test. Differentially expressed genes included genes involved in immune activation such as HLA-DQB1, MYD88, REL, and TNF-?. Our data suggest that future studies of distinct leukocyte subsets are warranted to identify possible surrogate biomarkers and may lead to the identification of novel interventions early in the disease course.

SUBMITTER: Schlachetzki JCM

PROVIDER: S-EPMC6050266 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A monocyte gene expression signature in the early clinical course of Parkinson's disease.

Schlachetzki Johannes C M JCM Prots Iryna I Tao Jenhan J Chun Hyun B HB Saijo Kaoru K Gosselin David D Winner Beate B Glass Christopher K CK Winkler Jürgen J

Scientific reports 20180717 1

Microglia are the main immune cells of the brain and express a large genetic pattern of genes linked to Parkinson's disease risk alleles. Monocytes like microglia are myeloid-lineage cells, raising the questions of the extent to which they share gene expression with microglia and whether they are already altered early in the clinical course of the disease. To decipher a monocytic gene expression signature in Parkinson's disease, we performed RNA-seq and applied the two-sample Kolmogorov-Smirnov ...[more]

PMID: 30018301

Similar Datasets

Project description:BackgroundThe search for biomarkers in Parkinson's disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.ResultsThe transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60-0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08-1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75-0.99), 19?S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60-0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14-1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. The performance of the five-gene classifier on the de novo PD individuals alone composing the early PD cohort (n?=?38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD?=?0.09)) in this cohort was higher than that of the early PD group (0.83 (SD?=?0.22)), suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer's disease (n?=?29).ConclusionsThe findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.

Dataset Information

A monocyte gene expression signature in the early clinical course of Parkinson's disease.

Publications

A monocyte gene expression signature in the early clinical course of Parkinson's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets