Document Detail


Uric acid as a CNS antioxidant.
MedLine Citation:
PMID:  20061611     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Gene L Bowman; Jackilen Shannon; Balz Frei; Jeffrey A Kaye; Joseph F Quinn
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of Alzheimer's disease : JAD     Volume:  19     ISSN:  1875-8908     ISO Abbreviation:  J. Alzheimers Dis.     Publication Date:  2010  
Date Detail:
Created Date:  2010-03-23     Completed Date:  2010-07-22     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  9814863     Medline TA:  J Alzheimers Dis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1331-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aged
Alzheimer Disease / prevention & control*
Antioxidants / pharmacology*,  therapeutic use*
Ascorbic Acid / cerebrospinal fluid,  pharmacology,  therapeutic use
Blood-Brain Barrier / drug effects
Brain / drug effects*
Female
Humans
Male
Uric Acid / cerebrospinal fluid,  pharmacology*,  therapeutic use*
Grant Support
ID/Acronym/Agency:
K23 AT004777/AT/NCCAM NIH HHS; K23 AT004777-02/AT/NCCAM NIH HHS; K23 AT004777-04/AT/NCCAM NIH HHS; K23AT004777/AT/NCCAM NIH HHS; L30 AT005424/AT/NCCAM NIH HHS; L30 AT005424-01/AT/NCCAM NIH HHS; P01 AT002034/AT/NCCAM NIH HHS; P01 AT002034-07/AT/NCCAM NIH HHS; P30 AG008017/AG/NIA NIH HHS; P30 AG008017-20/AG/NIA NIH HHS; P30 AG08017/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 268B43MJ25/Uric Acid; PQ6CK8PD0R/Ascorbic Acid
Comments/Corrections
Comment In:
J Alzheimers Dis. 2010;19(4):1337-8   [PMID:  20061607 ]

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