Introduction: Alzheimers disease (AD) is a neurodegenerative disease that is manifested by progressive loss of cognitive function. Neuroactive steroids and their metabolites have an important regulatory role in the nervous system, affect neuronal plasticity, response to stress, learning and memory and have a neuroprotective effect. One of the not fully elucidated risk factors for AD is impaired glucose tolerance/type 2 diabetes (T2D). It is well known that lower androgen levels contribute to the development of metabolic syndrome and T2D in males. In females, on the contrary, insulin resistance and T2D are associated with an excess of androgens. In previous studies, we have constructed a predictive model for the classification of AD patients based on levels of circulating steroids and their polar conjugates. We found lower androgen levels in AD patients regardless of sex.
Aim: The aim of this study was to examine whether the presence of T2D affects steroid hormone levels in female AD patients.
Methods: We compared the spectrum of steroid hormones in 3 groups of women: 1. women with AD and without T2D (n=10, median age 78 years), 2. women with AD and T2D (n=10, median age 78 years), 3. women without AD and without T2D (n=10, median age 77 years). The data were processed by GLM ANOVA and multidimensional regression using O2PLS method (Statgraphics 18×64, SIMCA v. 12.0).
Results: T2D-only women had higher androgen levels compared to women with AD and T2D (conjugated 7α-hydroxy-dehydroepiandrosterone, P=0.02, conjugated 7β-hydroxy-dehydroepiandrosterone, P=0.0008, 5-androstene-3β,7β,17β-triol, P<0.001, conjugated 5-androstene-3β,7α,17β-triol, P<0.001; 5α-androstane-3α,17β-diol, P=0.02). These results were confirmed by multidimensional regression analysis, which also found significantly higher levels of testosterone in T2D-only group compared to the other two groups. Between the two groups of patients with AD there were found no significant T2D-dependent differences in steroid hormone levels.
Conclusion: T2D in women increases androgen levels, but in AD patients these differences are not significant enough to affect the model for the classification of AD patients based on the circulating steroid hormones.
Supported by grants NV 18-01-00399, MH CR-DRO (EU 00023761).
18 - 21 May 2019
European Society of Endocrinology