Uric acid as a CNS antioxidant

Gene L. Bowman, Jackilen Shannon, Balz Frei, Jeffrey A. Kaye, Joseph F. Quinn

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

Oxidative damage is a consistent finding in a number of central nervous system (CNS) disorders. Uric acid (UA) is a potent hydrophilic antioxidant that is modified by diet and drug. Several lines of evidence suggest that plasma UA may modulate outcomes in neurologic disease, but little attention has been paid to CNS levels of UA. Our objective was to test the hypothesis that cerebrospinal fluid (CSF) UA is determined by plasma UA, modified by blood-brain barrier (BBB) integrity and associated with rate of cognitive decline in Alzheimer's disease (AD). Also, since UA and ascorbic acid may act as antioxidants for one another, we also explored a potential interaction between them in the brain. Thirty-two patients with mild to moderate AD (Mini-Mental Status Exam 19 ± 5) participated in a longitudinal biomarker study for one year involving standardized clinical assessments. CSF and blood were collected at baseline for UA, ascorbic acid, and albumin. Cognitive measures were collected at baseline and again one year later. CSF UA was independent of age, gender, and AD severity. CSF and plasma UA were positively correlated (r=0.669, p=0.001) and BBB impairment was associated with higher CSF levels of UA (p=0.028). Neither plasma nor CSF UA reached significant association with rates of cognitive decline over 1 year. CSF UA and CSF ascorbic acid were positively correlated (r=0.388, p=0.001). The hypothesis that CSF UA is determined by plasma UA and BBB integrity is supported, as is the hypothesis that UA and ascorbic acid are associated in CSF but not plasma. Adequately powered prospective studies would help assess any role for UA in primary and secondary prevention of AD.

Original languageEnglish (US)
Pages (from-to)1331-1336
Number of pages6
JournalJournal of Alzheimer's Disease
Volume19
Issue number4
DOIs
StatePublished - 2010

Keywords

  • Alzheimer's disease
  • Ascorbic acid
  • Blood-brain barrier
  • Cerebrospinal fluid
  • Uric acid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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