Abstract
Rationale
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).
Objectives
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.
Results
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.
Conclusion
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baulieu EE, Robel P, Fellous A, Duchossoy Y, Fontaine-Lenoir V, David S (2004) MAPREG: toward a novel approach of neuroprotection and treatment of Alzheimer's disease. J Mol Neurosci 24:63–65
Dubrovsky BO (2005) Steroids, neuroactive steroids and neurosteroids in psychopathology. Prog Neuropsychopharmacol Biol Psychiatry 29:169–192
Finn DA, Gee KW (1994) The estrus cycle, sensitivity to convulsants and the anticonvulsant effect of a neuroactive steroid. J Pharmacol Exp Ther 271:164–170
Frank C, Sagratella S (2000) Neuroprotective effects of allopregnenolone on hippocampal irreversible neurotoxicity in vitro. Prog Neuropsychopharmacol Biol Psychiatry 24:1117–1126
Frye CA, Lacey EH (2000) Progestins influence performance on cognitive tasks independent of changes in affective behavior. Psychobiology 8:550–563
Frye CA, Scalise TJ, Bayon LE (1998) Finasteride blocks the reduction in ictal activity produced by exogenous estrous cyclicity. J Neuroendocrinol 10:291–296
Frye CA, Sturgis JD (1995) Neurosteroids affect spatial/reference, working, and long-term memory of female rats. Neurobiol Learn Mem 64:83–96
Herzog AG, Frye CA (2003) Seizure exacerbation associated with inhibition of progesterone metabolism. Ann Neurol 53:390–391
Maurice T, Urani A, Phan VL, Romieu P (2001) The interaction between neuroactive steroids and the sigma1 receptor function: behavioral consequences and therapeutic opportunities. Brain Res Brain Res Rev 37:116–132
Rhodes ME, McCormick CM, Frye CA (2004) 3alpha,5alpha-THP mediates progestins' effects to protect against adrenalectomy-induced cell death in the dentate gyrus of female and male rats. Pharmacol Biochem Behav 78:505–512
Schumacher M, Weill-Engerer S, Liere P, Robert F, Franklin RJ, Garcia-Segura LM, Lambert JJ, Mayo W, Melcangi RC, Parducz A, Suter U, Carelli C, Baulieu EE, Akwa Y (2003) Steroid hormones and neurosteroids in normal and pathological aging of the nervous system. Prog Neurobiol 71:3–29
Stoffel-Wagner B (2001) Neurosteroid metabolism in the human brain. Eur J Endocrinol 145:669–679
Twist SJ, Taylor GA, Weddell A, Weightman DR, Edwardson JA, Morris CM (2000) Brain oestradiol and testosterone levels in Alzheimer's disease. Neurosci Lett 286:1–4
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Smith, C.D., Wekstein, D.R., Markesbery, W.R. et al. 3α,5α-THP: a potential plasma neurosteroid biomarker in Alzheimer's disease and perhaps non-Alzheimer's dementia. Psychopharmacology 186, 481–485 (2006). https://doi.org/10.1007/s00213-005-0186-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-005-0186-1