Neurosteroids as markers for alzheimer's disease
OwnerVassilios Papadopoulos, Rachel C. Brown +1inventors
InventorsVassilios Papadopoulos, Rachel C. Brown, Caterina Cascio
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Abstract
One of the major problems with the diagnosis and treatment of neurological diseases is the inability of clinicians to determine the onset of disease. The present invention describes methods and kits whereby the onset of neuropathology is detected by changes in the normal levels of neurosteroids, and particularly DHEA and its metabolic precursors, in the brain and serum.
Claims33
A method of detecting oxidative stress-mediated Dehydroepiandrosterone (DHEA) formation in a test sample of blood, body fluid or tissue comprising:
- (a) treating said test fluid or tissue with an agent that produces oxidative metabolites in a control fluid or tissue,
- (b) treating a control fluid or tissue with said agent, and
- (c) determining whether the quantities of DHEA in the test sample and in the control sample rise in response to said treatment,
- whereby a lack of response in the test sample relative to the control sample indicates that oxidative stress-mediated DHEA formation occurred previously in said test sample of body fluid.
A method of diagnosing the existence of a neuropathologic disorder in a patient comprising measuring the quantity of a neurosteroid in the CNS of said patient.
A kit for detecting oxidative stress-mediated Dehydroepiandrosterone (DHEA) formation in a test sample of blood, body fluid or tissue comprising a reagent that produces oxidative metabolites when contacted with said blood, body fluid or tissue.
A kit for detecting a neuropathologic disorder comprising a DHEA-specific antibody.
A method of increasing or causing DHEA synthesis by cells, comprising exposing said cells to β-amyloid peptide, wherein such exposure results in synthesis of DHEA.
A method of preventing or treating a neuropathology involving increased synthesis of DHEA comprising administering a compound that modulates the synthesis of DHEA by oligodendrocytes or astrocytes.
A screening assay for identifying drug candidates potentially useful for treating a neuropathology comprising:
- (a) exposing a composition comprising oligodendrocytes or astrocytes to a test compound to be screened for potential use in screening a neuropathology;
- (b) evaluating the effect of said compound on DHEA synthesis relative to an otherwise identical control composition containing oligodendrocytes or astrocytes but lacking said compound;
- and
- (c) identifying potentially useful compounds based on their modulating effect on DHEA synthesis.
Dependencies are inferred from the claim text.