Gender-Specific Neuroimmunoendocrine Aging in a Triple-Transgenic 3×Tg-AD Mouse Model for Alzheimer’s Disease and Its Relation with Longevity
Abstract
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 3×Tg-AD mice harboring PS1M146V, APPSwe and tauP301L 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 3×Tg-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 3×Tg-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.
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3xTg-AD males continue to experience higher rates of mortality relative to females.
“Despite this sex-specific phenotypic drift, 3xTg-AD males continue to experience higher rates of mortality relative to females [20, 21].”
3xTg-AD mice are one of the only models to develop both Aβ plaques and NFTs, in addition to exhibiting stark sexual dimorphism.
“They are one of the only models to develop both Aβ plaques and NFTs, in addition to exhibiting stark sexual dimorphism [18–22].”
These results align with published literature and reinforce the translatability of the 3xTg-AD model.
“Together, these results align with published literature [20, 21, 23, 24, 26, 27] and reinforce the translatability of the 3xTg-AD model.”
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Physical exercise neuroprotects ovariectomized 3xTg-AD mice through BDNF mechanisms
García-Mesa, Y., Pareja-Galeano, H., Bonet-Costa, V., Revilla, S., Gómez-Cabrera, M. C., Gambini, J., Giménez-Llort, L., Cristòfol, R., Viña, J., & Sanfeliu, C. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.03.021 · Cited by 68 · see citing works
Self-citationBarber, A. J., del Genio, C. L., Swain, A. B., Pizzi, E. M., Watson, S. C., Tapiavala, V. N., Zanazzi, G. J., & Gaur, A. B. (2024) · Alzheimer's Research & Therapy · doi:10.1186/s13195-024-01492-x · Cited by 41 · see citing works
- Authors
- Giménez-Llort, L., Arranz, L., Maté, I., & De la Fuente, M.
- Affiliations
- Universidad Complutense de Madrid (ES)
- Venue
- Neuroimmunomodulation
- Publisher
- S. Karger AG
- Published
- 2008
- Volume
- 15
- Issue
- 4-6
- Pages
- 331-343
- ISSN
- 1021-7401 (ISSN-L)
- 1423-0216
- OpenAlex
- W1978232373
- Cited by
- 91
- References
- 9
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 9 · 2023: 4 · 2022: 6 · 2021: 14 · 2020: 4 · 2019: 3 · 2018: 10 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 3 · 2012: 6
- FWCI
- 0.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImmunoModulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, aging, immunosenescence, sex differences, 3xTg-AD mice, longevity, P301L tau, neuroinflammation, endocrinology
- MeSH terms
- Aging, Alzheimer Disease, Animals, Corticosterone, Disease Models, Animal, Estrogens, Female, Hydrocortisone, Hypothalamo-Hypophyseal System, Inflammation, Longevity, Lymphocyte Activation, Lymphoid Tissue, Male, Mice, Transgenic, Neurosecretory Systems, Pituitary-Adrenal System, Sex Characteristics, Stress, Physiological, Neuroimmunomodulation, Cytokines, Mice
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