Serum Uric Acid Levels in Neurodegenerative Disorders: A Cross-Sectional Study

Aerqin, Qiaolifan; Jia, Shasha; Shen, Xue‐Ning; Li, Quan; Chen, Keliang; Ou, Ya‐Nan; Huang, Yu-Yuang; Dong, Qiang; Chen, Shufen; Yu, Jin‐Tai

doi:10.3233/jad-220432

Cited by 9 publications

(3 citation statements)

References 58 publications

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“…It functions as a special free radical inhibitor and can chelate metal ions like iron and copper besides acting as a radical scavenger ( 52 ). Previous studies have shown a significant decrease in serum UA in PD ( 53 ),but these observational studies have many limitations in clearly stating the causal relationship between UA and PD. Recently, minority studies had used Mendelian randomization, although it is not clear whether there is a causal link between the two.…”

Section: Discussionmentioning

confidence: 99%

Neurodegenerative disease and antioxidant biomarkers: A bidirectional Mendelian randomization study

Zhang

Zhao

et al. 2023

Front. Neurol.

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ObjectivePrevious observational studies have suggested that antioxidant imbalance is correlated with neurodegenerative diseases, while its cause–effect remains unclear. Thus, the goal of the present study is to explore the causal relationship between 11 antioxidant biomarkers and 3 most common neurodegenerative diseases [Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s disease (PD)].MethodsA bidirectional Mendelian randomization (MR) study was performed to investigate the causal effects by using 3 main methods (Variance Weighted (IVW), Weighted Median (WM), and MR-Egger regression) in the European population. The data of 11 antioxidant biomarkers were obtained from the open database by the most up-to-date Genome-Wide Association Studies (GWAS), the summary statistics of PD and ALS were obtained from the International Parkinson’s Disease Genomics Consortium (IPDGC) (33,674 cases, and 449,056 controls), and the International Amyotrophic Lateral Sclerosis Genomics Consortium (IALSC) (20,806 cases and 59,804 controls), respectively. For AD, we specifically used two recently published GWAS data, one from the International Genomics of Alzheimer’s Project (IGAP) (21,982 cases and 41,944 controls), and the other from a large meta-analysis (71,880 cases and 383,378 controls) as validation data.ResultsBased on the Bonferroni correction p < 0.0015, there was no significant causal evidence for the antioxidant biomarkers on neurodegenerative diseases, however, the reverse analysis found that AD was significantly related to the decrease in retinol (IVW: beta = −0.023, p = 0.0007; WM: beta = −0.025, p = 0.0121), while the same analysis was carried out between the AD validation database and retinol, the results were consistent (IVW: beta = −0.064, p = 0.025). Moreover, AD on Glutathione S-transferase (GST), PD on Glutathione Peroxidase (GPX) as well as PD on uric acid (UA) also indicated potential causal-and-effect associations (IVW: p = 0.025; p = 0.027; p = 0.021, respectively).ConclusionsThere was no sufficient evidence that antioxidant imbalance has a significant causal effect on neurodegenerative diseases. However, this study revealed that genetically predicted AD was significantly related to the decrease in retinol, which provides a new insight into previous research and indicates the possibility to regard retinol as potential biomarker for the diagnosis and progress of AD.

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Section: Discussionmentioning

confidence: 99%

Neurodegenerative disease and antioxidant biomarkers: A bidirectional Mendelian randomization study

Zhang

Zhao

et al. 2023

Front. Neurol.

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“…While hyperuricemia is linked to oxidative stress and associated with various diseases, lower uric acid levels correlate with neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Uric acid also has neuroprotective effects in Parkinson's disease models (34,35). Despite evidence suggesting a potential association between elevated uric acid and dementia risk, particularly in Alzheimer's disease, the underlying mechanisms remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Investigating the Therapeutic Potential of Uric Acid in Alzheimer's Disease: Insights from the cGMP-PKG Signaling Pathway

Li,

Jiang

et al. 2024

Preprint

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Background: Alzheimer's disease (AD) is characterized by neuroinflammation and oxidative stress, both contributing to disease progression. Uric acid (UA) has emerged as a potential therapeutic agent due to its anti-inflammatory and antioxidative properties. However, the precise mechanisms underlying UA's role in AD pathogenesis remain unclear. Methods: BV2 microglial cells were subjected to treatments with UA, lipopolysaccharide (LPS), or a combination of both. Analyses of gene expression profiling, protein assessment, ELISA, ROS assays, and proteomic analysis were performed. Statistical analyses involved one-way ANOVA followed by Dunnett's multiple comparison tests and Student’s unpaired t-test for group comparisons. Results: UA treatment markedly suppressed LPS-induced upregulation of NF-𝜅B and NLRP3 mRNA expression (p < 0.001). Inflammatory cytokine release (IL-1β and TNF𝜶) was reduced by up to 50% (p < 0.05) with UA treatment, while oxidative stress was mitigated, evidenced by an 84% reduction in ROS levels (p < 0.001) and a 32% increase in antioxidant enzyme activity (p < 0.01). Proteomic analysis unveiled significant alterations in key signaling pathways pertinent to AD pathology, including downregulation of cholesterol metabolism (p < 0.05) and upregulation of cGMP-PKG (p < 0.001) and Wnt signaling pathways (p < 0.001). Notably, UA treatment induced increased expression of Atp2b4, a pivotal regulator of calcium homeostasis, suggesting its potential role in mediating the observed antioxidative effects. Conclusions: UA exhibits promising anti-inflammatory and antioxidative effects in BV2 microglial cells, underscoring its potential as a therapeutic avenue for AD. These findings offer valuable insights into UA's molecular mechanisms and advocate for further investigation to validate its clinical efficacy in managing AD. Understanding UA's role in modulating neuroinflammatory pathways and oxidative stress could pave the way for novel therapeutic interventions in AD management.

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“…It plays a crucial role in protecting against oxidative stress by interacting with reactive oxygen species (ROS) and converting non-enzymatically to allantoin. [28][29][30] Oxidative stress is one of the major mechanisms involved in the pathophysiology of central nervous system inflammation and neurodegenerative diseases. In some studies, higher levels of uric acid have been associated with a reduced risk of neurodegenerative diseases such as Parkinson's and Alzheimer's.…”

Section: Introductionmentioning

confidence: 99%

EEG Power Spectral Density in NREM Sleep is Associated with the Degree of Hypoxia in Patients with Obstructive Sleep Apnea

Zhang,

Wang,

et al. 2023

NSS

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Purpose Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder. Research conducted on patients with OSA using electroencephalography (EEG) has revealed a noticeable shift in the overnight polysomnography (PSG) power spectrum. To better quantify the effects of OSA on brain function and to identify the most reliable predictors of pathological cortical activation, this study quantified the PSG power and its association with the degree of hypoxia in OSA patients. Patients and Methods This retrospective study recruited 93 patients with OSA. OSA patients were divided into three groups based on their apnea-hypopnea index (AHI) scores. The clinical characteristics and sleep macrostructure of these patients were examined, followed by an analysis of PSG signals. Power spectral density (PSD) in five frequency bands was analyzed during nonrapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, and wakefulness. Finally, correlation analysis was conducted to assess the relationships among PSD, PSG parameters, and serum levels of S100β and uric acid. Results Obstructive sleep apnea occurred during both the NREM and REM sleep phases. Except for a decrease in the duration of N2 sleep and an increase in the microarousal index, there were no significant differences in sleep architecture based on disease severity. Compared to the mild OSA group, the theta and alpha band PSD in the frontal and occipital regions during NREM sleep and wakefulness were significantly decreased in the moderate and severe OSA groups. Correlation analysis revealed that theta PSD in N1 and N3 stages were negatively correlated the AHI, oxygen desaturation index, SaO2<90% and microarousal index. Conclusion These findings imply that patients with more severe OSA exhibited considerable NREM hypoxia and abnormal brain activity in the frontal and occipital regions. Therefore, sleep EEG oscillation may be a useful neurophysiological indicator for assessing brain function and disease severity in patients with OSA.

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Serum Uric Acid Levels in Neurodegenerative Disorders: A Cross-Sectional Study

Cited by 9 publications

References 58 publications

Neurodegenerative disease and antioxidant biomarkers: A bidirectional Mendelian randomization study

Neurodegenerative disease and antioxidant biomarkers: A bidirectional Mendelian randomization study

Investigating the Therapeutic Potential of Uric Acid in Alzheimer's Disease: Insights from the cGMP-PKG Signaling Pathway

EEG Power Spectral Density in NREM Sleep is Associated with the Degree of Hypoxia in Patients with Obstructive Sleep Apnea

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