Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice
Open accessAbstract
We sought to determine if sex impacts the cognitive and neuropathological phenotype of the 3xTg-AD mice. We find that male and female 3xTg-AD mice show comparable impairments on Morris water maze (MWM) and inhibitory avoidance (IA) at 4 months. Shortly thereafter, however, the cognitive performance varies among the sexes, with females performing worse than males. These behavioral differences are not attributable to differences in Abeta or tau levels. The behavioral effect is transient as from 12 months onward, the disparity is no longer apparent. Because females perform worse than males on stressful tasks, we explored their corticosterone responses and find that young female 3xTg-AD mice show markedly heightened corticosterone response after 5 days of MWM training compared to age-matched male 3xTg-AD mice; this difference is no longer apparent in older mice. Thus, the enhanced corticosterone response of the young female mice likely underlies their poorer performance on stressful tasks.
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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].”
From Age, sex and Alzheimer’s disease: a longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimer’s patients (2024) · cites this paper as [19]
The Introduction reports that 3xTg-AD mice develop plaques and tangles, and the Results and Discussion describe age-dependent sex differences in cognition and stress response. The paper does not establish that they are one of the only models with both lesions; it also reports no significant sex difference in Aβ or tau pathology. (LLM, conf=0.87)
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- Authors
- Clinton, L. K., Billings, L. M., Green, K. N., Caccamo, A., Ngo, J., Oddo, S., McGaugh, J. L., & LaFerla, F. M.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- LaFerla, Frank M.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 28
- Issue
- 1
- Pages
- 76-82
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC2756084
- OpenAlex
- W1973802652
- Cited by
- 299
- References
- 8
- Citations by year
- 2026: 11 · 2025: 8 · 2024: 21 · 2023: 12 · 2022: 18 · 2021: 27 · 2020: 15 · 2019: 18 · 2018: 22 · 2017: 16 · 2016: 17 · 2015: 15 · 2014: 18 · 2013: 27 · 2012: 15
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Aging (AG0212982, F32AG024035, P50AG016573, F32 AG24035-01, R01AG021982, T32AG000096)
- National Institute of Mental Health (R01MH012526, MH12526, R56MH012526)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- 3xTg-AD mice, Alzheimer's disease, sex differences, sexual dimorphism, age differences, cognitive impairment, stress response, corticosterone, Morris water maze, passive avoidance, amyloid-beta, tau protein, sex differences in neurodegeneration
- MeSH terms
- Age Factors, Alzheimer Disease, Animals, Avoidance Learning, Brain, Cognition, Cognition Disorders, Corticosterone, Enzyme-Linked Immunosorbent Assay, Female, Immunohistochemistry, Male, Mice, Transgenic, Sex Characteristics, Stress, Psychological, Amyloid beta-Peptides, Maze Learning, Mice
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