Preliminary evidence of altered steroidogenesis in women with Alzheimer's disease: Have the patients OLDER adrenal zona reticularis?

Alzheimer's disease (AD) represents more than half of total dementias. Various factors including altered steroid biosynthesis may participate in its pathophysiology. We investigated how the circulating steroids (measured by GC-MS and RIA) may be altered in the presence of AD. Sixteen women with AD and 22 age and BMI-corresponding controls aged over 65 years were enrolled in the study. The steroid levels (47 steroids and steroid polar conjugates) and their ratios in AD female patients indicated increased CYP11A1 activity, weakened activity of the CYP17A1C17,20 lyase metabolic step and attenuated sulfotransferase SULT2A1 activity at higher activity of the CYP17A1 17-hydroxylase step. The patients showed diminished HSD3B2 activity for C21 steroids, abated conversion of 17-hydroxyprogesterone to cortisol, and significantly elevated cortisol. The women with AD had also attenuated steroid 7 alpha-hydroxylation forming immunoprotective Delta(5)-C19 steroids, attenuated aromatase activity forming estradiol that induces autoimmunity and a shift from the 3 beta-hydroxy-5 alpha/beta-reduced C19 steroids to their neuroinhibitory and antiinflammatory GABAergic 3 alpha-hydroxy-counterparts and showed higher levels of the 3 alpha-hydroxy-5 alpha/beta-reduced C21 steroids and pregnenolone sulfate (improves cognitive abilities but may be both protective and excitotoxic). Our preliminary data indicated functioning of alternative backdoor pathway in women with AD showing higher levels of both 5 alpha/beta-reduced C21 steroids but reduced levels of both 5 alpha/beta-reduced C21 steroids, which implied that the alternative backdoor pathway might include both 5 alpha- and 5 beta-reduced steroids. Our study suggested relationships between AD status in women based on the age of subjects and levels of 10 steroids measured by GC MS. (C) 2015 Elsevier Ltd. All rights reserved.