3α,5α-THP: a potential plasma neurosteroid biomarker in Alzheimer's disease and perhaps non-Alzheimer's dementia
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- Smith, C.D., Wekstein, D.R., Markesbery, W.R. et al. Psychopharmacology (2006) 186: 481. doi:10.1007/s00213-005-0186-1
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A plasma biomarker for neurodegenerative disease is desirable because blood is relatively simple to obtain compared with other biological samples such as cerebrospinal fluid. Recent literature suggests that neurosteroid metabolism may be altered in Alzheimer's disease (AD).
We sought to measure the plasma levels of seven steroids to assess their potential as biomarkers for dementia and AD. Methods: Steroids were measured using validated radioimmunoassay methods in AD (n=15), non-AD dementia (n=4), and control subjects (n=20). Demented subjects were in the mild-to-moderate stages of illness. Measurements were done blind to subject status in an independent laboratory.
The notable finding was the significantly lower 5α-pregnan-3α-ol-20-one (3α,5α-THP) level in demented subjects compared with controls (25% decrease; p=0.004); 3α,5α-THP was the only one of the steroids demonstrating an effect of dementia.
Lowered 3α,5α-THP levels appear promising as a biomarker in dementia, but further work is needed to establish the sensitivity and specificity of these findings in AD.