*4.2. Down-Regulation of HPA Axis Endocrine Status in Female 3xTg-AD Mice*

At the endocrine level, mild hypercortisolemia is observed in AD patients [45], and the stimulation of the HPA can result in peripheral immune depression [46]. In the present work, the HPA axis exhibited sexual dimorphism, with higher levels of plasma corticosterone in females than males. The AD–genotype effect reduced plasmatic corticosterone levels in 3xTg-AD females, attenuating the sexual dimorphism in one degree of magnitude. These data agree with our first report in 15-month NTg and 3xTg-AD [12]. In all groups, the corticosterone levels were higher than those reported at 15 months, which could be due to the animals' increased stress response to the experimental design, especially observed in females [47]. These corticosterone levels were similar to those observed in NTg and 3xTg-AD mice after chronic treatment with caffeine and vehicle [48].
