No evidence for systemic oxidant stress in Parkinson's or Alzheimer's disease

Abstract

Oxidant stress secondary to dopamine metabolism has been proposed as a pathogenic factor in the development of Parkinson's disease. Biochemical abnormalities extending beyond the central nervous system have been identified in patients with this condition. Previous investigators have found abnormally elevated concentrations of the lipid peroxidation product, malondialdehyde, in the plasma and serum of patients with Parkinson's disease. We attempted to replicate these findings but controlled for other factors that could influence malondialdehyde levels. We detected no significant elevations in mean serum malondialdehyde concentrations in either levodopa-treated or untreated patients with Parkinson's disease, compared to normal controls; similarly, no elevation was found in a group of patients with dementia of Alzheimer's type. On the other hand, a group of subjects with diabetes mellitus but no neurodegenerative disease had significantly elevated mean serum malondialdehyde levels, consistent with previous studies of diabetic patients. Autoxidation is one of the two major routes by which dopamine and dopa metabolism may generate oxygen free radicals. We analyzed the autoxidation product of dopa, 5-S-cysteinyl-dopa, in the plasma of these same groups of patients with neurodegenerative disease and normal controls; no significant differences were identified. Serum concentrations of two other antioxidant substances, alpha-tocopherol and uric acid, were also statistically similar in these groups. In conclusion, analysis of several blood products relevant to oxidant stress, including malondialdehyde, 5-S-cysteinyl-dopa, alpha-tocopherol, and uric acid, failed to distinguish patients with Parkinson's disease or dementia of Alzheimer's type from controls.

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

“…Similarly, another small (43 PD cases) study [657] observed no differences in serum uric acid levels between PD cases, Alzheimer cases, and controls. However, a recent study found lower levels of serum uric acid in PD cases than controls (p value 0.03) [658].…”

Age-related changes in nitric oxide activity, cyclic GMP, and TBARS levels in platelets and erythrocytes reflect the oxidative status in central nervous system

“…Although not a consensus (Ahlskog et al 1995), the presence of increased oxidative stress at peripheral level in AD was evidenced in some studies. Kawamoto et al (2005) detected in platelets and erythrocytes the involvement of ONOO − anion in aging and AD.…”

Electrochemical Analysis of Protein Nitrotyrosine and Dityrosine in the Alzheimer Brain Indicates Region-Specific Accumulation

“…One previous study reports decreased uric acid in AD CSF (Tohgi et al, 1993), whereas another reports increased uric acid in AD CSF (Degrell and Niklasson, 1988). Measurements of serum uric acid in AD are similarly contradictory (Maesaka et al, 1993;Ahlskog et al, 1995). Interestingly, uric acid reportedly protects rodents against motor dysfunction and tyrosine nitration in the experimental allergic encephalomyelitis model of multiple sclerosis (Hooper et al, 1997), suggesting that clinical symptoms of specific neurological disorders might respond to alterations in this compound.…”