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KMID : 0960920030020010011
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Dementia and Neurocognitive Disorders
2003 Volume.2 No. 1 p.11 ~ p.16
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Clinical Significance of Cerebrospinal Fluid Neurosteroid Level in Alzheimer’s Disease and Vascular Dementia
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Kwak Yong-Tae
Morfin Robert
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Abstract
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Background: The role of the neurosteroid DHEA in degenerative disease is unknown, although a neurodegenerative disorder such as Alzheimer’s disease (AD) has higher dehydroepiandrosterone (DHEA) levels in cerebrospinal fluid (CSF) than that of controls. Increased DHEA production in brain involves alternative pathways, induced by reactive oxygen species, and activated by the beta-amyloid protein. Since human brain is known to metabolize DHEA into DHEA sulfate (DHEAS), 7alpha-hydroxy-DHEA, 7beta-hydroxy-DHEA and 16alpha-hydroxy-DHEA, it is possible that DHEA accumulation in brain results from increased production of DHEA and decreased production of such metabolites. To investigate the clinical significance of neurosteroids and test such an hypothesis, we compared the concentrations of CSF neurosteroid levels between patients of dementia and controls.
Methods: We compared the concentrations of CSF levels of pregnenolone (PREG), PREG sulfate (PREGS), DHEA, DHEAS, 7alpha-hydroxy-DHEA, 7beta-hydroxy-DHEA and 16alpha-hydroxy-DHEA among 14 patients with AD, 8 patients with vascular dementia (VD) and 12 controls. After CSF sample was measured by high performance liquid chromatography, consequently, 7alpha-hydroxy-DHEA, 7beta-hydroxy-DHEA was measured by RIA, and 16alpha-hydroxy-DHEA, PREGS was measured by ELISA.
Results: DHEA CSF levels were significantly increased (p=0.005), and DHEAS level was significantly decreased in AD and VD (p=0.004) while other metabolite levels were not significantly changed. Steroid level ratios such as DHEA/(7alpha-hydroxy-DHEA+7beta-hydroxy-DHEA), 16alpha-hydroxy-DHEA/DHEA, gave significant differences between diseased and control patients (p<0.000, p=0.004, respectively).
Conclusions: These results indicate that DHEA found in CSF does not help protecting brain from patients of dementia and are neither better sulfated nor better hydroxylated at 7alpha, 7beta and 16alpha-positions than in controls. These results indicate that, though some CSF neurosteroid levels are significantly different between demented patients and controls, clinical usefulness for differential diagnosis of AD and VD may have limited value.
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KEYWORD
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Dehydroepiandrosterone (DHEA), Dehydroepiandrosterone sulfate (DHEAS), Neurosteroid, Alzheimer’s disease, Vascular
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