The urate and xanthine concentrations in the cerebrospinal fluid in patients with vascular dementia of the Binswanger type, Alzheimer type dementia, and Parkinson's disease

Tohgi, Hideo; Abe, Takashi; Takahashi, Satoshi; Kikuchi, Toshihiro

doi:10.1007/bf02261005

Cited by 57 publications

(43 citation statements)

References 26 publications

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“…It is therefore possible that the uric acid decline in AD brain reflects, or possibly contributes to, AD-related neurodegeneration. 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).…”

Section: Discussionmentioning

confidence: 98%

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

et al. 1998

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HPLC with electrochemical array detection (HPLC-ECD) was used to quantify 3,3Ј-dityrosine (diTyr) and 3-nitrotyrosine (3-NO 2 -Tyr) in four regions of the human brain that are differentially affected in Alzheimer's disease (AD). DiTyr and 3-NO 2 -Tyr levels were elevated consistently in the hippocampus and neocortical regions of the AD brain and in ventricular cerebrospinal fluid (VF), reaching quantities five-to eightfold greater than mean concentrations in brain and VF of cognitively normal subjects. Uric acid, a proposed peroxynitrite scavenger, was decreased globally in the AD brain and VF. The results suggest that AD pathogenesis may involve the activation of oxidant-producing inflammatory enzyme systems, including nitric oxide synthase.Key words: HPLC; nitrotyrosine; dityrosine; Alzheimer's disease; protein oxidation; inflammation The Alzheimer's disease (AD) brain exhibits region-specific patterns of amyloid plaque deposition, neurofibrillary tangle (NFT) accumulation, and neuron death. The limbic system and association areas of the neocortex show the most pronounced histopathological alterations in AD, whereas cortical somatosensory and cerebellar neurons are relatively spared (Pearson et al., 1985;Henderson and Finch, 1989;Braak and Braak, 1994). Recent models of AD attempt to link disease progression with an inflammatory component combined with increased oxidative stress (Rogers et al., 1996). C lassical hallmarks of inflammation such as edema and neutrophil infiltration are not acknowledged characteristics of the AD brain, although numerous correlates of inflammation are present. Acute-phase reactants such as C-reactive protein, major histocompatibility complex glycoproteins, complement, monocyte chemoattractants, interleukin-1, and interleukin-6 are elevated in AD brain in spatial association with neuritic plaques (Griffin et al., 1989McGeer et al., 1989;Bauer et al., 1991;Strauss et al., 1992;C arpenter et al., 1993; Wood et al., 1993;Iwamoto et al., 1994;Mrak et al., 1995;Pereira et al., 1996;Rogers et al., 1996;Sheng et al., 1996). Reactive microglia, f unctionally similar to monocytes, are increased in the AD brain and concentrate near senile plaques (McGeer et al., 1987;Haga et al., 1989;Itagaki et al., 1989; Carpenter et al., 1993;MacKenzie et al., 1995).Enhanced oxidative stress in the AD brain is manifested by increases in protein carbonyl content and lipid and DNA oxidation products and by inactivation of sensitive enzymes (Oliver et al., 1987;C. Smith et al., 1991C. Smith et al., , 1992Mecocci et al., 1993;Balazs and Leon, 1994;Chen et al., 1994;Hensley et al., 1995; Lovell et al., 1995;M. Smith et al., 1996;Butterfield et al., 1997;Lyras et al., 1997;Sayre et al., 1997). Correlation between oxidative and inflammatory biomarkers has not been achieved in the AD brain, although the activation of an inflammatory response might, in large part, explain AD brain oxidation. For instance, activated microglia release superoxide (O 2 ⅐ Ϫ ) and hydrogen peroxide (H 2 O 2 ) (Colton et al., 1994), whe...

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Section: Discussionmentioning

confidence: 98%

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

et al. 1998

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“…The association of low-normal serum urate levels with Parkinson's disease and multiple sclerosis has led to proposals that higher PUA protects neurons from toxic effects of peroxynitrite (7,(41)(42)(43). However, urate concentration in brain is much lower than in plasma (7,44,45); urate is a poor scavenger of peroxynitrite (46)(47)(48); and reactions of urate with free radicals have pro-as well as antioxidant consequences (46,47,49,50). Moreover, significantly raising serum urate concentration for 2 years was of no benefit in patients with relapsing-remitting multiple sclerosis (51).…”

Section: Discussionmentioning

confidence: 99%

Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo

Hershfield

Roberts²,

Ganson³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

121

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A high plasma urate concentration (PUA), related to loss of urate oxidase in evolution, is postulated to protect humans from oxidative injury. This hypothesis has broad clinical relevance, but support rests largely on in vitro data and epidemiologic associations. Pegloticase therapy generates H 2 O 2 while depleting urate, offering an in vivo test of the antioxidant hypothesis. We show that erythrocytes can efficiently eliminate H 2 O 2 derived from urate oxidation to prevent cell injury in vitro; during therapy, disulfide-linked peroxiredoxin 2 dimer did not accumulate in red blood cells, indicating that their peroxidase capacity was not exceeded. To assess oxidative stress, we monitored F2-Isoprostanes (F2-IsoPs) and protein carbonyls (PC), products of arachidonic acid and protein oxidation, in plasma of 26 refractory gout patients receiving up to five infusions of pegloticase at 3-wk intervals. At baseline, PUA was markedly elevated in all patients, and plasma F2-IsoP concentration was elevated in most. Pegloticase infusion rapidly lowered mean PUA to ≤1 mg/dL in all patients, and PUA remained low in 16 of 21 patients who completed treatment. F2-IsoP levels did not correlate with PUA and did not increase during 15 wk of sustained urate depletion. There also was no significant change in the levels of plasma PC. Because refractory gout is associated with high oxidative stress in spite of high PUA, and profoundly depleting uric acid did not increase lipid or protein oxidation, we conclude that urate is not a major factor controlling oxidative stress in vivo.

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“…A postmortem study of 4 PD cases showed decreased levels of uric acid in substantia nigra compared to controls [655]. Another study of 11 PD cases found no differences in cerebrospinal fluid levels of uric acid between cases and controls [656].…”

Section: Uric Acid and Goutmentioning

confidence: 98%

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

et al. 2011

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The urate and xanthine concentrations in the cerebrospinal fluid in patients with vascular dementia of the Binswanger type, Alzheimer type dementia, and Parkinson's disease

Cited by 57 publications

References 26 publications

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

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

Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo

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

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