Sex dimorphism profile of Alzheimer’s disease-type pathologies in an APP/PS1 mouse model
Abstract
Alzheimer's disease (AD) is the most common form of dementia among the elderly, characterized by parenchymal and vascular beta-amyloid (Aβ) burden, tau pathology, neuroinflammation, and loss of neurons and synapses. There is a clear sex difference in the prevalence of AD. However, sex differences in AD-type pathologies have not been systematically documented. Applying 12-month-old female and male APP/PS1 mice as a model, we investigated the sex dimorphism in these major pathological indices. Compared with male APP/PS1 mice, the females exhibited higher parenchymal Aβ burdens, with the sex difference in hippocampus being the most significant. Female APP/PS1 mice had more severe cerebral amyloid angiopathy and subsequent microhemorrhage. In addition, female APP/PS1 mice also showed higher levels of phosphorylated tau and proinflammatory cytokines, more severe astrocytosis and microgliosis, and greater neuronal and synaptic degenerations. The present study systematically described a sex dimorphism in AD-type pathologic indices, suggesting that gender should be taken into account in designing studies involving these pathological indices and when interpreting the relevant findings in those studies.
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Prior observations in AD mouse models and human epidemiology have implicated sex as a modifier of AD manifestation and progression.
“Prior observations in AD mouse models (Jiao et al., 2016) and human epidemiology (Altmann et al., 2014; Li and Singh, 2014; Mayeux and Stern, 2012) have implicated sex as a modifier of AD manifestation and progression.”
From Meta-Analysis of the Alzheimer’s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models (2020) · cites this paper as Jiao et al., 2016
Our results are consistent with prior observations of sex effects in both mice and humans.
“Our results are consistent with prior observations in both mice (Jiao et al., 2016) and humans (Altmann et al., 2014; Li and Singh, 2014; Mayeux and Stern, 2012; Mathys et al., 2019; Sala Frigerio et al., 2019).”
From Meta-Analysis of the Alzheimer’s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models (2020) · cites this paper as Jiao et al., 2016
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- Authors
- Jiao, S.-S., Bu, X.-L., Liu, Y.-H., Zhu, C., Wang, Q.-H., Shen, L.-L., Liu, C.-H., Wang, Y.-R., Yao, X.-Q., & Wang, Y.-J.
- Affiliations
- Army Medical University (CN)
- Corresponding author
- Wang, Yan-Jiang
- Venue
- Neurotoxicity Research
- Published
- 2015-12-26
- Volume
- 29
- Issue
- 2
- Pages
- 256-266
- ISSN
- 1029-8428 (ISSN-L)
- 1476-3524
- OpenAlex
- W2289382754
- Cited by
- 129
- References
- 11
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 20 · 2023: 8 · 2022: 18 · 2021: 18 · 2020: 9 · 2019: 7 · 2018: 9 · 2017: 10 · 2016: 1
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurotoxicity Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81471296, 81200988)
- 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, sexual dimorphism, APP/PS1 mice, amyloid-beta, cerebral amyloid angiopathy, microhemorrhages, tau phosphorylation, neuroinflammation, inflammatory cytokines, astrocyte activation, microglial activation, neurodegeneration, synaptic degeneration, hippocampus, vascular pathology
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Encephalitis, Female, Humans, Male, Mice, Transgenic, Neurons, Phosphorylation, Sex Characteristics, Synapses, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Cerebral Amyloid Angiopathy, tau Proteins, Inflammation Mediators, Mice, Presenilin-1
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