RT Journal Article
T1 Premature Neuroimmune and Redox-Inflammatory Breakdown at the Prodromal Stage in Male and Female Triple-Transgenic Alzheimer’s Disease Mice
A1 Giménez Llort, Lydia
A1 Vida, Carmen
A1 Félix Escalera, Judith
A1 Quer Palomas, Silvia
A1 Manassra, Rashed
A1 Fuente Del Rey, María Mónica De La
AB Background/Objectives: Homeostatic (nervous, immune and endocrine) systems and their communications network are crucial for health and aging rate. We previously reported behavioral and peritoneal leukocyte function alterations and oxidative-inflammatory stress in young female triple-transgenic (3xTg) mice for Alzheimer’s disease (AD). Here, the deterioration of the homeostatic systems and their interplay was investigated, in an integrated way, at prodromal stages and in both sexes of 3xTg-AD mice. Methods: An integrative analysis of the behavioral profile, peripheral immune splenic and thymic leukocyte functions, splenic oxidative-inflammatory state, and plasmatic corticosterone in both sexes of 3xTg-AD mice at 4 months of age was compared to that of age- and sex-matched NTg counterparts. Results: The prodromal stage of 3xTg-AD, characterized by anxiety-like behaviors and disrupted exploration, was aligned with reduced chemotaxis, natural killer activity, and lymphoproliferation—especially in the spleen. In addition, 3xTg-AD mice exhibited lower anti-inflammatory (IL-10) and higher pro-inflammatory (IL-2, IL-1β, and TNF-α) cytokine concentrations and oxidative stress (higher oxidants and lower antioxidants). Several of these alterations displayed sex-dependent differences (worse in males). However, no differences in corticosterone were found. Conclusions: These findings suggest that neuroimmune and redox-inflammatory dysfunctions, indicative of premature aging, emerge at the prodromal stage of AD, preceding corticosterone changes, unveiling a time lag in the neuroimmunoendocrine alterations in these animals. They may act as early indicators of premature aging in AD pathology and provide potential targets for sex-specific prodromal intervention.
PB MDPI
SN 2079-9721
YR 2026
FD 2026-02-09
LK https://hdl.handle.net/20.500.14352/135057
UL https://hdl.handle.net/20.500.14352/135057
LA eng
NO Giménez-Llort, L., Vida, C., Félix, J., Quer-Palomas, S., Manassra, R., & De la Fuente, M. (2026). Premature Neuroimmune and Redox-Inflammatory Breakdown at the Prodromal Stage in Male and Female Triple-Transgenic Alzheimer’s Disease Mice. Diseases, 14(2). https://doi.org/10.3390/DISEASES14020061
NO This research was funded by FIS ISC3 PI10/00283, RETICEF (Red de Envejecimiento y Fragilidad) ISC3 RD06/0013/0003, Research Group of Translational Behavioral Neuroscience UAB-GE-260408, and the Research Group of UCM-CM (ENEROINN 910379), Generalitat de Catalunya 2021 SGR-00529.
NO Instituto de Salud Carlos III
NO Universitat Autònoma de Barcelona
NO Universidad Complutense de Madrid
NO Comunidad de Madrid
NO Generalitat de Catalunya
DS Docta Complutense
RD 29 abr 2026