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

Article Type: Research Article

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. Show more

Keywords: Alzheimer's disease, ascorbic acid, blood-brain barrier, cerebrospinal fluid, uric acid

DOI: 10.3233/JAD-2010-1330

Citation: Journal of Alzheimer's Disease, vol. 19, no. 4, pp. 1331-1336, 2010

Authors: Quinn, Joseph | Suh, Jung | Moore, M. Milar | Kaye, Jeffrey | Frei, Balz

Article Type: Research Article

Abstract: Levels of several antioxidants and related markers were measured in cerebrospinal fluid (CSF) and plasma of 10 Alzheimer's disease (AD) patients and 10 controls. Daily dosage of vitamin C was significantly correlated with both plasma (R=0.662; p=0.0015) and CSF level (R=0.639, p=0.0024). Plasma and CSF vitamin C levels were also highly correlated R=0.793, p<0.0001). Similarly, daily dosage of Vitamin E was significantly correlated with plasma vitamin E (R=0.681; p=0.0009) and showed a trend toward correlation with CSF vitamin E (R=0.422, p=0.06). There were no significant differences between groups in absolute CSF or plasma levels of any analyte. However, the CSF: …plasma ratio of vitamin C was significantly greater in the AD patients compared to the controls (p=0.048). In a subset of AD patients, hippocampal volume was significantly correlated with plasma (R2 =0.833; p=0.004) and CSF (R2 =0.603; p=0.04) vitamin C levels, and inversely correlated with CSF:plasma vitamin C ratio (R2 =0.717; p=0.016). We conclude that oral vitamin C supplements are delivered to the brain, and speculate that the increased CSF: plasma ratio of vitamin~C in AD reflects increased antioxidant consumption by the AD brain. Show more

DOI: 10.3233/JAD-2003-5406

Citation: Journal of Alzheimer's Disease, vol. 5, no. 4, pp. 309-313, 2003

Authors: Bowman, Gene L. | Dodge, Hiroko | Frei, Balz | Calabrese, Carlo | Oken, Barry S. | Kaye, Jeffrey A. | Quinn, Joseph F.

Article Type: Research Article

Abstract: The brain maintains high levels of ascorbic acid (AA) despite a concentration gradient favoring diffusion from brain to peripheral tissues. Dietary antioxidants, including AA, appear to modify the risk of Alzheimer's disease (AD). The objective of this study was to test the hypothesis that neurodegeneration in AD is modified by brain levels of AA. Thirty-two patients with mild to moderate AD participated in a biomarker study involving standardized clinical assessments over one year. Cerebrospinal fluid (CSF) and serum were collected at baseline for AA and albumin content. Cognitive measures were collected at baseline and one year. CSF and plasma AA …failed to predict cognitive decline independently, however, CSF: plasma AA ratio did. After adding CSF Albumin Index (an established marker of blood-brain barrier integrity) to the regression models the effect of CSF: plasma AA ratio as a predictor of cognitive decline was weakened. CSF: plasma AA ratio predicts rate of decline in AD. This relationship may indicate that the CSF: plasma AA ratio is an index of AA availability to the brain or may be an artifact of a relationship between blood-brain barrier impairment and neurodegeneration. Show more

Keywords: Albumin, Alzheimer's disease, antioxidants, ascorbic acid, blood-brain barrier, cerebrospinal fluid, cognitive decline, vitamin C

DOI: 10.3233/JAD-2009-0923

Citation: Journal of Alzheimer's Disease, vol. 16, no. 1, pp. 93-98, 2009