Baseline Plasma C-Reactive Protein Concentrations and Motor Prognosis in Parkinson Disease

Umemura, Atsushi; Oeda, Tomoko; Yamamoto, Kenji; Tomita, Satoshi; Kohsaka, Masayuki; Park, Kwiyoung; Sugiyama, Hiroshi; Sawada, Hideyuki

doi:10.1371/journal.pone.0136722

Cited by 37 publications

(25 citation statements)

References 37 publications

(37 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Longitudinal studies are necessary to investigate whether inflammatory marker changes predate a more aggressive disease course. Only 1 previous study, to our knowledge, has adopted such a longitudinal approach, investigating the role of CRP in 375 PD cases and reporting an association with more rapid motor deterioration (UPDRS‐III), which is in keeping with our findings.…”

Section: Discussionsupporting

confidence: 88%

“…Furthermore cultured peripheral blood mononuclear cells from PD patients produce higher levels of inflammatory cytokines in response to stimulation with lipopolysaccharides compared with controls, and these cytokine levels correlate with motor severity of disease . More recently, an association between higher plasma C‐reactive protein (CRP) levels and more rapid motor progression in PD has also been reported …”

mentioning

confidence: 99%

“…8 More recently, an association between higher plasma C-reactive protein (CRP) levels and more rapid motor progression in PD has also been reported. 19 This study investigated a panel of immune markers in serum samples from a large incident PD cohort and an age-matched control group, to ascertain whether there was any association with disease status and measures of disease severity and progression over a subsequent 36 months of follow-up. Thus, for the first time we explore the profile and relevance of serum immune markers in newly diagnosed PD cases with the aim of further informing our understanding of the relationship between peripheral immune responses and disease progression, and evaluating whether these easily accessible markers may constitute useful biomarkers in PD.…”

mentioning

confidence: 99%

See 2 more Smart Citations

S erum immune markers and disease progression in an incident P arkinson's disease cohort ( ICICLE‐PD )

et al. 2016

View full text Add to dashboard Cite

BackgroundThe immune system is a promising therapeutic target for disease modification in Parkinson's disease (PD), but appropriate immune‐related biomarkers must be identified to allow patient stratification for trials and tracking of therapeutic effects. The objective of this study was to investigate whether immune markers in peripheral blood are candidate prognostic biomarkers through determining their relationship with disease progression in PD.MethodsSerum samples were collected in incident PD cases and age‐matched controls. Subjects were clinically evaluated at baseline and 18 and 36 months. Ten cytokines and C‐reactive protein were measured, with data reduction using principal‐component analysis, and relationships between component scores and motor (MDS Unified Parkinson's Disease Rating Scale — part 3) and cognitive (Mini Mental State Examination [MMSE]) measures of disease severity/progression were investigated.ResultsTNF‐α, IL1‐β, IL‐2, and IL‐10 were higher in PD (n = 230) than in controls (n = 93), P ≤ 0.001). Principal‐component analysis of log‐transformed data resulted in a 3‐component solution explaining 51% of the variance. Higher “proinflammatory” and lower “anti‐inflammatory” component scores were associated with more rapid motor progression over 36 months (P < 0.05), and higher “proinflammatory” component scores were associated with lower MMSE at all times (P < 0.05). Multiple linear regression analysis with adjustment for covariates confirmed “anti‐inflammatory” component score was the strongest predictor of slower motor progression (β = −0.22, P = 0.002), whereas proinflammatory cytokines were associated with lower baseline MMSE (β = −0.175, P = 0.007).ConclusionsSerum immune marker profile is predictive of disease progression in PD and hence a potential prognostic biomarker. However, interventional trials are needed to clarify whether peripheral immune changes causally contribute to the progression of PD. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

show abstract

Section: Discussionsupporting

confidence: 88%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

S erum immune markers and disease progression in an incident P arkinson's disease cohort ( ICICLE‐PD )

et al. 2016

View full text Add to dashboard Cite

show abstract

“…A possible explanation for increased Ser(P)‐1292 LRRK2 levels in PD patients with poorer scores on assessments of cognitive performance and activities of daily living may be increased inflammation in the patients with aggressive progression of disease. Elevations in several cytokines have been observed in the CSF of PD patients as well as increased plasma C‐reactive protein levels with correlations to PD severity . Multivariate modeling for most of these inflammation markers also observed significant gender effects, potentially in line with observations from this study.…”

Section: Discussionsupporting

confidence: 87%

Ser(P)‐1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease

et al. 2016

View full text Add to dashboard Cite

Background Mutations in Leucine-rich repeat kinase 2 (LRRK2) enhance levels of autophosphorylated LRRK2 protein and are the most common known cause of inherited Parkinson disease (PD). LRRK2 has been further implicated in susceptibility to idiopathic PD in genetic association studies. Objective To compare autophosphorylated Ser(P)-1292 LRRK2 levels from biobanked urine samples with clinical data in PD and controls. Methods Ser(P)-1292 LRRK2 levels were measured from urine exosome fractions from 79 PD and 79 neurologically healthy controls enrolled into the Parkinson Disease Biomarker Program at the University of Alabama at Birmingham. Results Ser(P)-1292 LRRK2 levels were higher in males than females (p<0.0001) and elevated in PD compared to controls (p=0.0014). Ser(P)-1292 LRRK2 levels were higher in PD cases with worse cognition and correlated with poor performance in MoCA (r=−0.2679 [−0.4628, −0.0482]), MDS-UPDRS subscales 1 and 2 (r=0.2239 [0.0014, 0,4252], 0.3404 [0.1276, 0.5233] respectively), Epworth Sleepiness Scale (r=0.3215 [0.1066, 0.5077]), and Modified Schwab and England Activities of Daily Living Scales (r=−0.4455 [−0.6078, −0.2475]). Ser(P)-1292 LRRK2 levels predicted those with worse cognitive impairment in PD patients with some success (c=0.73). Conclusions Urinary exosome Ser(P)-1292 LRRK2 levels are elevated in idiopathic PD and correlated with the severity of cognitive impairment and difficultly in accomplishing activities of daily living. These results implicate biochemical changes in LRRK2 in idiopathic PD.

show abstract

“…43 In the same context of vascular risk and metabolic changes we found elevated C-reactive protein a predictor of cognitive decline in PD, but not for UPDRS III as has been previously described. 44 C-reactive protein is known to mediate the link between glucose and uric acid 45 and has been shown to be a predictor of life expectancy and death in PD. 46 Further important predictors for faster motor progression were neurofilament light chains in CSF.…”

Section: Discussionmentioning

confidence: 99%

Baseline predictors for progression 4 years after Parkinson's disease diagnosis in the De Novo Parkinson Cohort (DeNoPa)

et al. 2018

View full text Add to dashboard Cite

Objectives The objectives of this study were to investigate (1) the annual rate of progression of motor and cognitive symptoms and (2) baseline predictors of different modalities for this progression in early Parkinson's disease (PD) when compared with healthy controls. Methods A total of 135 de novo PD and 109 healthy controls (of the De Novo Parkinson cohort) were investigated at baseline and after 24 and 48 months. To delineate motor progression and cognitive decline, the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale part III (MDS‐UPDRS III) and the Mini‐Mental Status Examination (MMSE) were selected. Baseline variables used to predict progression included sociodemographic factors, comorbidities, motor/nonmotor symptoms, polysomnography, MRI, and laboratory biomarkers in serum and CSF. Results Symptoms worsened over 4 years in PD with an annual change of 1.8 points on the MDS‐UPDRS III and 0.2 points on the MMSE. Baseline predictors of worse progression of motor symptoms in PD included male sex, orthostatic blood pressure drop, diagnosis of coronary artery disease, arterial hypertension, elevated serum uric acid, and CSF neurofilament light chain. Predictors of cognitive decline in PD included previous heavy alcohol abuse, current diagnoses of diabetes mellitus, arterial hypertension, elevated periodic limb movement index during sleep, decreased hippocampal volume by MRI, higher baseline levels of uric acid, C‐reactive protein, high density lipoprotein (HDL) cholesterol, and glucose levels. Conclusion Cardiovascular risk factors, deregulated blood glucose, uric acid metabolism, and inflammation were identified as risk markers for faster disease progression. Our panel of risk parameters needs validation during our continuing follow‐up and also in independent patient cohorts. © 2018 International Parkinson and Movement Disorder Society

show abstract

Baseline Plasma C-Reactive Protein Concentrations and Motor Prognosis in Parkinson Disease

Cited by 37 publications

References 37 publications

S erum immune markers and disease progression in an incident P arkinson's disease cohort ( ICICLE‐PD )

S erum immune markers and disease progression in an incident P arkinson's disease cohort ( ICICLE‐PD )

Ser(P)‐1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease

Baseline predictors for progression 4 years after Parkinson's disease diagnosis in the De Novo Parkinson Cohort (DeNoPa)

Contact Info

Product

Resources

About