Gender-specific neuroimmunoendocrine aging in a triple-transgenic 3xTg-AD mouse model for Alzheimer's disease and its relation with longevity.

In the present work, we briefly review the evidence on the key role played by the neuroimmunoendocrine network in the etiopathogenesis of Alzheimer's disease (AD) and provide new behavioral, immune and endocrinological data obtained on old male and female triple-transgenic 3xTg-AD mice harboring PS1(M146V), APP(Swe) and tau(P301L) transgenes in contrast to wild-type animals. The results indicate that several aspects of the impairment of the neuroimmunoendocrine network that occurs with aging are more evident in the 3xTg-AD mice, especially in males. This supports the hypothesis of a premature immunosenescence as a pathogenically relevant factor in AD which was found to be enhanced in the 3xTg-AD males, suggesting that this could also be responsible for the increased morbidity and mortality of these subjects. Therefore, future research on strategies that could improve the immune system and the other regulatory systems, such as the nervous and the endocrine system, as well as their communication, could have preventive and/or therapeutical effects on that disease. The results also show the relevance of gender differences that should be taken into consideration in both basic and clinical research for assessing new strategies for the control of AD.