Oxidative Imbalance in Different Neurodegenerative Diseases with Memory Impairment

Abstract

Background: Byproducts of oxidative metabolic reactions could play a role in the pathogenesis of several neurodegenerative diseases (ND) including Alzheimer’s disease (AD). We designed a study aimed at investigating a large set of oxidative and antioxidant markers in a sample of patients affected by different forms of dementia or memory impairment. Methods: Serum levels of coenzyme Q₁₀, malondialdehyde (MDA), the total, oxidized and reduced forms of glutathione (GStot, GSSG and GSH, respectively), reactive oxygen species, anti-oxidized low-density lipoprotein antibodies and antioxidant power (PAO) were investigated in patients affected by AD, mild cognitive impairment, dementia with Lewy bodies and Parkinson’s disease with dementia. The patient sample (n = 66) was compared with healthy subjects (HC; n = 62), and a comparison across pathological subgroups was also performed. A multivariate logistic regression model was implemented in order to calculate an algorithm model for predicting the risk of developing a neurodegenerative disorder. Results: The comparison between the memory deficit (MD) group and HC showed a significant difference for MDA (MD: 6.3 ± 2.8 µg/l; HC: 9.1 ± 4.9 µg/l; p = 1.7 × 10^–6), GStot (MD: 260.4 ± 62.6 mg/l; HC: 306.5 ± 60.7 mg/l; p = 2.2 × 10^–5), GSH (MD: 208.9 ± 68.4 mg/l; HC: 295.3 ± 101.3 mg/l; p = 2.2 × 10^–7) and PAO (MD: 1,066.5 ± 247.7 µmol; HC: 954.9 ± 200.4 µmol; p = 0.8 × 10^–3). By contrast, no differences in the levels of the studied markers were detected across the different forms of ND. An older age, higher levels of PAO, lower levels of GSH and MDA and the use of cardiovascular or antidepressant drugs were the most important factors associated with the carrier ship of neurodegenerative disorder. Conclusion: To our knowledge, this is the first study reporting similar oxidative imbalance in different forms of memory impairment, regardless of the specific etiology. Low GSH levels could be considered as a favorable factor in ND; at the same time it could be suggested that higher levels of PAO represent a counteracting mechanism against an increased oxidative stress. The association between vascular risk factors, depressive status and cognitive impairment is in line with findings in the literature.

Plasma antioxidant status and motor features inde novoChinese Parkinson's disease patients

“…GSH plays a vital role in protecting the body through eliminating the excessive ROS via the complex reduction and conjugation reactions [33]. In this study, we observed a decreased plasma level of GSH in de novo PD patients, which was in line with several previous studies [10,12,14,15,24,34] and further emphasized the role of GSH in PD. Nevertheless, the mechanism underlying the depleting of GSH in PD is not fully clear [33] and future studies are necessitated to address this issue .…”

Potential biomarkers relating pathological proteins, neuroinflammatory factors and free radicals in PD patients with cognitive impairment: a cross-sectional study

“…Microglial expression of inducible nitric oxide synthase leads to excessive NO generation [23]. Previous studies indicate an important role of oxidative stress on cognitive impairment in neurodegenerative diseases [7,8,34]; however, less attention is paid to the role of free radicals on PD-CI. In this investigation, •OH level in CSF in PD-CI group is significantly increased comparing with control group, and is negatively correlated with MoCA score, suggesting a pivotal effect of oxidative stress in PD-CI and •OH may be a potential indicator of PD-CI deterioration.…”

Antioxidant Status andAPOEGenotype As Susceptibility Factors for Neurodegeneration in Alzheimer's Disease and Vascular Dementia

“…Uric acid and ascorbic acid (along with albumin) are the major soluble contributors among the non-enzymatic antioxidants to serum TAS, whereas vitamin A, tocopherols/tocotrienols (vitamin E), and a-and b-carotene are lipid soluble and key mediators for limiting lipid oxidation. Decreased TAS in serum of AD has been demonstrated in numerous studies, suggesting an overall decrease in AD, 41,42 even though antioxidant enzymes solely were found unchanged. However, the notion that antioxidant capacity is significantly elevated in AD and directly related to disease severity has been highlighted also in a recent post-mortem case-control study.…”