Affiliations: [a] Department of Neurology, Layton Center for Aging and Alzheimer's Disease Research, Oregon Health & Science University, Portland, OR, USA | [b] Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, OR, USA | [c] Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
Correspondence:
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Correspondence to: Gene L. Bowman, N.D., Oregon Health & Science University, 3181 SW Sam Jackson Park Road, CR-131, Portland, Oregon 97239 USA. Tel.: +1 503 494 6976; Fax: +1 503 494 7499; E-mail: bowmang@ohsu.edu.
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.
