Sex-based differences in the activation of peripheral blood monocytes in early Parkinson disease.
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ABSTRACT:
SUBMITTER: Carlisle SM
PROVIDER: S-EPMC8044127 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo examine potential sex differences in nonmotor symptoms (NMS) among drug-naive patients with Parkinson disease (PD), and to identify NMS that can best differentiate patients with early PD from controls.MethodsOur cross-sectional analysis included 414 newly diagnosed, untreated patients with PD (269 men and 145 women) and 188 healthy controls (121 men and 67 women) in the Parkinson's Progression Markers Initiative Study. NMS were measured using well-validated instruments covering sleep, olfactory, neurobehavioral, autonomic, and neuropsychological domains.ResultsMale and female patients with PD were fairly comparable on motor presentations but differed on several nonmotor features. Male patients with PD had significantly more pronounced deficits in olfaction (p = 0.02) and in certain cognitive measurements (all p < 0.01) than female patients, whereas female cases experienced higher trait anxiety (p = 0.02). Multiple stepwise logistic regression analysis showed that the combination of NMS measures-University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), and state anxiety from the State-Trait Anxiety Inventory-effectively differentiated patients with PD from controls with an area under the receiver operating characteristic curve (AUC) of 0.913 (95% confidence interval [CI]: 0.89-0.94). UPSIT, MoCA, and SCOPA-AUT were the most predictive NMS measurements in men (AUC = 0.919; 95% CI: 0.89-0.95) as compared to UPSIT, MoCA, and REM Sleep Behavior Disorder Screening Questionnaire in women (AUC = 0.903; 95% CI: 0.86-0.95).ConclusionsOur analysis revealed notable sex differences in several nonmotor features of patients with de novo PD. Furthermore, we found a parsimonious NMS combination that could effectively differentiate de novo cases from healthy controls.
| S-EPMC4451049 | biostudies-literature
Project description:Parkinson disease (PD) is a progressive neurodegenerative disorder that is 1.5 times more common in males than in females. While motor progression tends to be more aggressive in males, little is known about sex difference in cognitive progression. We tested the hypothesis that there are sex differences in cognitive dysfunction in non-demented PD. We evaluated 84 participants (38 females) with PD and 59 controls (27 females) for demographic variables and cognitive function, including attention, working memory, executive function, and processing speed. Multivariate ANOVA revealed no significant differences between groups for demographic variables, including age, years of education, global cogntition, daytime sleepiness, predicted premorbid IQ, UPDRS score, PD phenotype, or disease duration. For cognitive variables, we found poorer performance in males versus females with PD for measures of executive function and processing speed, but no difference between male and female controls. Specifically, PD males showed greater deficits in Verbal Fluency (category fluency, category switching, and category switching accuracy), Color Word Interference (inhibition), and speed of processing (SDMT). There were no differences in measures of working memory or attention across sex and inconsistent findings for switching. Our data indicate that males with PD have significantly greater executive and processing speed impairments compared to females despite no differences in demographic variables or other measures of disease severity. Our findings are consistent with the steeper slope of disease progression reported in males with PD.
| S-EPMC7142103 | biostudies-literature
Project description:Genomes of men and women differ in only a limited number of genes located on the sex chromosomes, whereas the transcriptome is far more sex-specific. Identification of sex-biased gene expression will contribute to understanding the molecular basis of sex-differences in complex traits and common diseases.Sex differences in the human peripheral blood transcriptome were characterized using microarrays in 5,241 subjects, accounting for menopause status and hormonal contraceptive use. Sex-specific expression was observed for 582 autosomal genes, of which 57.7% was upregulated in women (female-biased genes). Female-biased genes were enriched for several immune system GO categories, genes linked to rheumatoid arthritis (16%) and genes regulated by estrogen (18%). Male-biased genes were enriched for genes linked to renal cancer (9%). Sex-differences in gene expression were smaller in postmenopausal women, larger in women using hormonal contraceptives and not caused by sex-specific eQTLs, confirming the role of estrogen in regulating sex-biased genes.This study indicates that sex-bias in gene expression is extensive and may underlie sex-differences in the prevalence of common diseases.
| S-EPMC3904696 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) play an important role in many neurological diseases and can serve as biomarkers for these diseases. However, the information about circRNAs in Parkinson disease (PD) remained limited. In this study, we aimed to determine the circRNAs expression profile in PD patients and discuss the significance of circRNAs in the diagnosis of PD.Methods and resultsUsing RNA-sequencing in peripheral blood RNAs, we showed that a significant number of mRNAs or circRNAs were differentially expressed between PD patients and normal controls (NCs), which included 273 up-regulated and 493 down-regulated mRNAs, and 129 up-regulated and 282 down-regulated circRNAs, respectively. Functional analysis was performed using the Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis, and the results showed that the second most enriched KEGG pathway was PD. These data suggest that the levels of mRNAs and circRNAs in peripheral blood could be potentially used as biomarkers for PD. In addition, we correlated mRNAs and circRNAs by constructing a competing endogenous RNA (ceRNA) network in PD. The resulted-in ceRNA network included 10 differentially expressed mRNAs from PD pathway, 13 predicted miRNAs, and 10 differentially expressed circRNAs.ConclusionCollectively, we first characterized the expression profiles of circRNAs and mRNAs in peripheral blood from PD patients and proposed their possible characters in the pathogenesis of PD. These results provided valuable insights into the clues underlying the pathogenesis of PD.
| S-EPMC8202568 | biostudies-literature
Project description:BackgroundThe prevalence of Alzheimer's disease (AD) varies based on gender. Due to the lack of early stage biomarkers, most of them are diagnosed at the terminal stage. This study aimed to explore sex-specific signaling pathways and identify diagnostic biomarkers of AD.MethodsMicroarray dataset for blood was obtained from the Gene Expression Omnibus (GEO) database of GSE63060 to conduct differentially expressed genes (DEGs) analysis by R software limma. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene set enrichment analysis (GSEA) were conducted. Immune checkpoint gene expression was compared between females and males. Using CytoHubba, we identified hub genes in a protein-protein interaction network (PPI). Then, we evaluated their distinct effectiveness using unsupervised hierarchical clustering. Support vector machine (SVM) and ten-fold cross-validation were used to further verify these biomarkers. Lastly, we confirmed our findings by using another independent dataset.ResultsA total of 37 female-specific DEGs and 27 male-specific DEGs were identified from GSE63060 datasets. Analyses of enrichment showed that female-specific DEGs primarily focused on energy metabolism, while male-specific DEGs mostly involved in immune regulation. Three immune-checkpoint-relevant genes dysregulated in males. In females, however, these eight genes were not differentially expressed. SNRPG, RPS27A, COX7A2, ATP5PO, LSM3, COX7C, PFDN5, HINT1, PSMA6, RPS3A and RPL31 were regarded as hub genes for females, while SNRPG, RPL31, COX7C, RPS27A, RPL35A, RPS3A, RPS20 and PFDN5 were regarded as hub genes for males. Thirteen hub genes mentioned above was significantly lower in both AD and mild cognitive impairment (MCI). The diagnostic model of 15-marker panel (13 hub genes with sex and age) was developed. Both the training dataset and the independent validation dataset have area under the curve (AUC) with a high value (0.919, 95%CI 0.901-0.929 and 0.803, 95%CI 0.789-0.826). Based on GSEA for hub genes, they were associated with some aspects of AD pathogenesis.ConclusionDEGs in males and females contribute differently to AD pathogenesis. Algorithms combining blood-based biomarkers may improve AD diagnostic accuracy, but large validation studies are needed.
| S-EPMC9531459 | biostudies-literature
Project description: Not available
| S-EPMC10084516 | biostudies-literature
Project description:BackgroundThe role of sex in the outcomes of patients with peripheral arterial disease (PAD) has been poorly studied. We sought to investigate differences in the long-term adverse cardiovascular and limb outcomes between men and women with PAD.MethodsWe conducted a population-based cohort study with up to 7 years of follow-up using linked administrative databases in Ontario, Canada. Patients aged 40 years or older who visited a vascular surgeon between Apr. 1, 2004, and Mar. 31, 2007 (index date), and carried a diagnosis of PAD comprised the study cohort. The primary outcome was a composite of death or hospital admission for stroke or myocardial infarction. Secondary outcomes included lower limb amputation or revascularization. We used Cox proportional hazards modelling to compute unadjusted hazard ratios (HRs) and HRs adjusted for baseline covariates.ResultsA total of 6915 patients were studied, of whom 2461 (35.6%) were women. No significant differences in the risk of the primary outcome were observed between men and women (adjusted HR 0.99 [95% confidence interval (CI) 0.92-1.05]). Women were less likely than men to undergo minor amputation (adjusted HR 0.73 [95% CI 0.62-0.85]) and arterial bypass surgery (adjusted HR 0.82 [95% CI 0.71-0.94]) but were more likely to be admitted to hospital for acute myocardial infarction (adjusted HR 1.15 [95% CI 1.00-1.31]). There were no sex differences in the rates of major amputation or transluminal percutaneous angioplasty.InterpretationWe identified no significant differences in the composite risk of major adverse cardiovascular events between women and men with PAD, although our findings suggest men may be at increased risk for adverse limb events compared with women. Cardiovascular health campaigns should focus on both women and men to promote early diagnosis and management of PAD.
| S-EPMC4866931 | biostudies-literature
Project description:Background and purposeDeficits in tactile perception are common in patients with PD. However, the neural mechanisms have not been previously reported in the early stages. This study aims to investigate how the brain activity and connectivity changed under tactile perception at early Parkinsonian state by using functional MR imaging.Materials and methodsTwenty-one patients with early PD and 22 age- and sex-matched controls were recruited and scanned under a passive tactile stimulation task. Within-group and between-group activation maps were acquired, and regions of interest were defined according to the group-comparison result. This was followed by a functional connectivity analysis based on the graph theory.ResultsWe found that in the PD group, bilateral sensorimotor cortex was hypoactive during the task, whereas the hyperactive regions were mainly in bilateral prefrontal cortex, bilateral cerebellum, and contralateral striatum. There was a significant decrease of total connectivity degree in ipsilateral SMA in PD, which was negatively correlated with the Unified Parkinson's Disease Rating Scale score. Furthermore, the connection strengths among the areas of prefrontal cortex, striatum, and cerebellum were increased.ConclusionsThis study illustrated that early PD was associated with not only altered brain activation but also changed functional connectivity in tactile perception. The most significant impairment was in SMA, whereas striato-prefrontal and cerebello-prefrontal loops may play a compensatory role in early PD tactile function.
| S-EPMC7966011 | biostudies-literature
Project description:BackgroundGenetic mutations in beta-glucocerebrosidase (GBA) represent the major genetic risk factor for Parkinson's disease (PD). GBA participates in both the endo-lysosomal pathway and the immune response, two important mechanisms involved in the pathogenesis of PD. However, modifiers of GBA penetrance have not yet been fully elucidated.MethodsWe characterized the transcriptomic profiles of circulating monocytes in a population of patients with PD and healthy controls (CTRL) with and without GBA variants (n = 23 PD/GBA, 13 CTRL/GBA, 56 PD, 66 CTRL) and whole blood (n = 616 PD, 362 CTRL, 127 PD/GBA, 165 CTRL/GBA). Differential expression analysis, pathway enrichment analysis, and outlier detection were performed. Ultrastructural characterization of isolated CD14+ monocytes in the four groups was also performed through electron microscopy.ResultsWe observed hundreds of differentially expressed genes and dysregulated pathways when comparing manifesting and non-manifesting GBA mutation carriers. Specifically, when compared to idiopathic PD, PD/GBA showed dysregulation in genes involved in alpha-synuclein degradation, aging and amyloid processing. Gene-based outlier analysis confirmed the involvement of lysosomal, membrane trafficking, and mitochondrial processing in manifesting compared to non-manifesting GBA-carriers, as also observed at the ultrastructural levels. Transcriptomic results were only partially replicated in an independent cohort of whole blood samples, suggesting cell-type specific changes.ConclusionsOverall, our transcriptomic analysis of primary monocytes identified gene targets and biological processes that can help in understanding the pathogenic mechanisms associated with GBA mutations in the context of PD.
| S-EPMC9386994 | biostudies-literature
Project description:ObjectiveTo examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples).MethodsWhole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks.ResultsA gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was identified with the training cohort and successfully replicated in both an independent validation cohort (area under the curve [AUC] = 0.79, p = 7.13E-6) and a subsequent independent test cohort (AUC = 0.74, p = 4.2E-4). Network analysis of the signature revealed gene enrichment in pathways, including metabolism, oxidation, and ubiquitination/proteasomal activity, and misregulation of mitochondria-localized genes, including downregulation of COX4I1, ATP5A1, and VDAC3.ConclusionsWe present a large-scale study of PD gene expression profiling. This work identifies a reliable blood-based PD signature and highlights the importance of large-scale patient cohorts in developing potential PD biomarkers.
| S-EPMC5644465 | biostudies-literature