Abstract
Introduction: Heme oxygenase-1 (HO-1) is a 32 kDa stress-response protein implicated in the pathogenesis of Parkinson’s disease (PD). Biliverdin is derived from heme through a reaction mediated by HO-1 and protects cells from oxidative stress. However, iron and carbon monoxide produced by the catabolism of HO-1 exert detrimental effects on patients with PD. The purpose of this study was to determine whether plasma HO-1 levels represent a biomarker of PD and to further explore the underlying mechanism of increased HO-1 levels by applying voxel-based morphometry (VBM).Methods: We measured plasma HO-1 levels using an enzyme-linked immunosorbent assay (ELISA) in 156 subjects, including 81 patients with early- and advanced-stage PD and 75 subjects without PD. The analyses were adjusted to control for confounders such as age, sex, and medication. We analyzed T1-weighted magnetic resonance imaging (MRI) data from 74 patients with PD using VBM to elucidate the association between altered brain volumes and HO-1 levels. Then, we compared performance on MMSE sub-items between PD patients with low and high levels of HO-1 using Mann-Whitney U tests.Results: Plasma HO-1 levels were significantly elevated in PD patients, predominantly those with early-stage PD, compared with controls (p < 0.05). The optimal cutoff value for patients with early PD was 2.245 ng/ml HO-1 [area under the curve (AUC) = 0.654]. Plasma HO-1 levels were unaffected by sex, age, and medications (p > 0.05). The right hippocampal volume was decreased in the subset of PD patients with high HO-1 levels (p < 0.05). A weak correlation was observed between right hippocampal volume and plasma HO-1 levels (r = −0.273, p = 0.018). There was no difference in total MMSE scores between the low- and high-HO-1 groups (p > 0.05), but the high-HO-1 group had higher language scores than the low-HO-1 group (p < 0.05).Conclusions: Plasma HO-1 levels may be a promising biomarker of early PD. Moreover, a high plasma concentration of the HO-1 protein is associated with a reduction in right hippocampal volume.
Highlights
Heme oxygenase-1 (HO-1) is a 32 kDa stress-response protein implicated in the pathogenesis of Parkinson’s disease (PD)
Parkinson’s disease (PD) is a movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies induced by the aggregation of α-synuclein
The inclusion criteria were as follows: (1) a diagnosis of PD was made by an experienced neurologist; and (2) PD was diagnosed according to the United Kingdom Brain Bank Clinical Diagnostic Criteria (Hughes et al, 1992)
Summary
Heme oxygenase-1 (HO-1) is a 32 kDa stress-response protein implicated in the pathogenesis of Parkinson’s disease (PD). Parkinson’s disease (PD) is a movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies induced by the aggregation of α-synuclein. More than half of dopaminergic neurons are typically lost before a patient is diagnosed with PD. The long preclinical phase of PD offers the potential to administer disease-modifying treatments; an accessible biomarker that reflects the process of neurodegeneration is needed to diagnose the disease and predict disease progression in individual patients. A reliable biomarker would have great potential to help distinguish patients with PD from healthy persons, in the early stages of the disease
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