Antioxidant and inflammatory biomarkers for the identification of prodromal Parkinson's disease

Campolo, Jonica; Maria, Renata De; Cozzi, Lorena; Parolini, Marina; Bernardi, Stefano; Proserpio, Paola; Nobili, Lino; Gelosa, Giorgio; Piccolo, I.; Agostoni, Elio; Trivella, Maria Giovanna; Marraccini, Paolo

doi:10.1016/j.jns.2016.09.050

Cited by 19 publications

(7 citation statements)

References 37 publications

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“…The authors suggested that low GSH concentrations may be a promising blood biomarker for an early PD diagnosis. 23 However, the cross-sectional design, the small sample size, and the fact that pPD was not defined using the MDS-proposed pPD probability score but, rather, considering only one prodromal marker (RBD), limit the robustness and generalizability of the results. Our findings support the potential role of plasma GSH as a biomarker during the early stages of PD, as we demonstrated its relationship with pPD probability trajectories in a random sample of community-dwelling older adults.…”

Section: Discussionmentioning

confidence: 99%

“…In a cross‐sectional study including 15 participants with PD, 11 with idiopathic RBD (ie, a prodromal PD marker), and 12 healthy controls, blood reduced GSH (but not plasma GSH) concentrations were independently associated with overt PD and RBD. The authors suggested that low GSH concentrations may be a promising blood biomarker for an early PD diagnosis 23 . However, the cross‐sectional design, the small sample size, and the fact that pPD was not defined using the MDS‐proposed pPD probability score but, rather, considering only one prodromal marker (RBD), limit the robustness and generalizability of the results.…”

Section: Discussionmentioning

confidence: 99%

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Plasma Glutathione and Prodromal Parkinson's Disease Probability

et al. 2021

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Background A decrease in glutathione (GSH) levels is considered one of the earliest biochemical changes in Parkinson's disease (PD). Objective The authors explored the potential role of plasma GSH as a risk/susceptibility biomarker for prodromal PD (pPD) by examining its longitudinal associations with pPD probability trajectories. Methods A total of 405 community‐dwelling participants (median age [interquartile range] = 73.2 [7.41] years) without clinical features of parkinsonism were followed for a mean (standard deviation) of 3.0 (0.9) years. Results A 1 μmol/L increase in plasma GSH was associated with 0.4% (95% confidence interval [CI], 0.1%–0.7%; P = 0.017) less increase in pPD probability for 1 year of follow‐up. Compared with participants in the lowest GSH tertile, participants in the highest GSH tertile had a 12.9% (95% CI, 22.4%–2.2%; P = 0.020) slower rate of increase of pPD probability for 1 year of follow‐up. Conclusion Plasma GSH was associated with pPD probability trajectories; therefore, it might assist in the identification of individuals who are likely to reach the threshold for pPD diagnosis more rapidly. © 2021 International Parkinson and Movement Disorder Society

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Plasma Glutathione and Prodromal Parkinson's Disease Probability

et al. 2021

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“…In neutrophil granulocytes, PD patients were found to have altered mitochondrial mass and membrane potential, as well as increased oxidative stress . Prigione et al (2006) found increased total ROS levels in PD patient PBMCs compared with controls, and a recent pilot study demonstrated lower whole‐blood levels of reduced glutathione in RBD as well as PD patients …”

Section: Discussionmentioning

confidence: 99%

Mitochondrial dysfunction and increased glycolysis in prodromal and early Parkinson's blood cells

et al. 2018

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Background: Although primarily a neurodegenerative process, there is increasing awareness of peripheral disease mechanisms in Parkinson's disease. To investigate disease processes in accessible patient cells, we studied peripheral blood mononuclear cells in recently diagnosed PD patients and rapid eye movement‐sleep behavior disorder patients who have a greatly increased risk of developing PD. We hypothesized that peripheral blood mononuclear cells may recapitulate cellular pathology found in the PD brain and investigated these cells for mitochondrial dysfunction and oxidative stress. Methods: Peripheral blood mononuclear cells were isolated and studied from PD patients, rapid eye movement‐sleep behavior disorder patients and age‐ and sex‐matched control individuals from the well‐characterized Oxford Discovery cohort. All participants underwent thorough clinical assessment. Results: Initial characterization showed that PD patients had elevated levels of CD14 + monocytes and monocytes expressing C‐C motif chemokine receptor 2. Mitochondrial dysfunction and oxidative stress were increased in PD patient peripheral blood mononuclear cells, with elevated levels of mitochondrial reactive oxygen species specifically in patient monocytes. This was combined with reduced levels of the antioxidant superoxide dismutase in blood cells from PD patients and, importantly, also in rapid eye movement‐sleep behavior disorder patients. This mitochondrial dysfunction was associated with a concomitant increase in glycolysis in both PD and rapid eye movement‐sleep behavior disorder patient blood cells independent of glucose uptake or monocyte activation. Conclusions: This work demonstrates functional bioenergetic deficits in PD and rapid eye movement‐sleep behavior disorder patient blood cells during the early stages of human disease. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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“…In a similar manner, the treatment further increased the already-high levels of the anti-inflammatory cytokine IL-10 in PBMCs. In addition, we also tested neopterin, a sensitive marker of immune system activation for neurodegenerative disorders such as Parkinson's disease [42], which was not previously reported in X-ALD. We found elevated levels of neopterin in the CSF before treatment; these levels were significantly decreased with antioxidant treatment in all the subjects from whom CSF was available (Fig.…”

Section: Inflammatory Markersmentioning

confidence: 99%

Biomarker Identification, Safety, and Efficacy of High-Dose Antioxidants for Adrenomyeloneuropathy: a Phase II Pilot Study

et al. 2019

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X-Adrenoleukodystrophy (X-ALD) and its adult-onset, most prevalent variant adrenomyeloneuropathy (AMN) are caused by mutations in the peroxisomal transporter of the very long-chain fatty acid ABCD1. AMN patients classically present spastic paraparesis that can progress over decades, and a satisfactory treatment is currently lacking. Oxidative stress is an early culprit in X-ALD pathogenesis. A combination of antioxidants halts the clinical progression and axonal damage in a murine model of AMN, providing a strong rationale for clinical translation. In this phase II pilot, open-label study, 13 subjects with AMN were administered a high dose of α-tocopherol, N-acetylcysteine, and α-lipoic acid in combination. The primary outcome was the validation of a set of biomarkers for monitoring the biological effects of this and future treatments. Functional clinical scales, the 6-minute walk test (6MWT), electrophysiological studies, and cerebral MRI served as secondary outcomes. Most biomarkers of oxidative damage and inflammation were normalized upon treatment, indicating an interlinked redox and inflammatory homeostasis. Two of the inflammatory markers, MCP1 and 15-HETE, were predictive of the response to treatment. We also observed a significant decrease in central motor conduction time, together with an improvement or stabilization of the 6MWT in 8/10 subjects. This study provides a series of biomarkers that are useful to monitor redox and pro-inflammatory target engagement in future trials, together with candidate biomarkers that may serve for patient stratification and disease progression, which merit replication in future clinical trials. Moreover, the clinical results suggest a positive signal for extending these studies to phase III randomized, placebo-controlled, longer-term trials with the actual identified dose. ClinicalTrials.gov Identifier: NCT01495260

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Antioxidant and inflammatory biomarkers for the identification of prodromal Parkinson's disease

Cited by 19 publications

References 37 publications

Plasma Glutathione and Prodromal Parkinson's Disease Probability

Plasma Glutathione and Prodromal Parkinson's Disease Probability

Mitochondrial dysfunction and increased glycolysis in prodromal and early Parkinson's blood cells

Biomarker Identification, Safety, and Efficacy of High-Dose Antioxidants for Adrenomyeloneuropathy: a Phase II Pilot Study

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