Peripheral neuroactive steroids may be as good as the steroids in the cerebrospinal fluid for the diagnostics of CNS disturbances.

To compare the predictivity of the neuroactive steroids in the cerebrospinal fluid and peripheral blood for the diagnostics of CNS disturbances, eighteen unconjugated steroids were quantified in the cerebrospinal fluid (CSF) from the 3rd ventricle and 18 unconjugated steroids and 7 steroid polar conjugates were measured in the serum using GC-MS and RIA. Eight postmenopausal women (56-78 years of age) and 7 men (22-88 years of age) with hydrocephalus were enrolled in the study. The sensitivity of the method ranged from low femtogram to low picogram levels depending on the steroid fragmentation pattern. Using multivariate regression, a model for simultaneous prediction of the CSF steroids from the serum steroids was completed. Then, the penetrability of the individual steroids across the blood-brain-barrier was evaluated and the sources of various brain steroids were estimated. Our data show that a part of the steroids may be synthesized de novo in the CNS. However, substantial part of the steroid metabolites may be synthesized in the CNS from the steroid precursors or directly transported from the periphery. The CNS in situ synthesis and transport from periphery might be complementary in some cases, i.e. brain synthesis might provide minimum level of steroids, which are indispensable for the CNS functions.

Hippocampal glucose metabolism is associated with cerebrospinal fluid estrogen levels in postmenopausal women with Alzheimer's disease.

Animal studies indicate that estrogens, such as 17beta-estradiol (E(2)), may enhance hippocampal metabolism and function. In postmenopausal Alzheimer's disease (AD) patients, cerebrospinal fluid (CSF) E(2) levels were significantly lower than in non-demented controls. This finding was inversely correlated with CSF beta-amyloid levels. To address the potential impact of this finding, E(2) levels in CSF were correlated with regional cerebral [18F]2-fluoro-2-deoxy-D-glucose (FDG) uptake as measured using positron emission tomography (PET) in six postmenopausal AD patients. CSF E(2) levels were determined using an electro-chemiluminescence-immunoassay on the Roche Elecsys 2010 immunoassay analyzer. Basic image processing was done by MEDx, using SPM routines for spatial normalization and statistics. CSF E(2) levels were significantly correlated with cerebral glucose metabolism in the left hippocampus. This is the first clinical study indicating an association between CSF E(2) concentration and hippocampal glucose metabolism in postmenopausal women with AD.