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Cited by 122Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

The behavioural and neuropathologic sexual dimorphism and absence of MIP-3α in tau P301S mouse model of Alzheimer’s disease

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Sun, Yao, Guo, Yongqing, Feng, Xuejian, Jia, Meng, Ai, Ning, Dong, Yue, Zheng, Yayuan, Fu, Lu +6 more·2020·Journal of Neuroinflammation
DOI 10.1186/s12974-020-01749-wPMC PMC7041244

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Abstract

Background: Tau hyper-phosphorylation has been considered a major contributor to neurodegeneration in Alzheimer’s disease (AD) and related tauopathies, and has gained prominence in therapeutic development for AD. To elucidate the pathogenic mechanisms underlying AD and evaluate therapeutic approaches targeting tau, numerous transgenic mouse models that recapitulate critical AD-like pathology have been developed. Tau P301S transgenic mice is one of the most widely used mouse models in AD research. Extensive studies have demonstrated that sex significantly influences AD pathology, behavioral status, and therapeutic outcomes, suggesting that studies using mouse models of AD must consider sex- and age-related differences in neuropathology, behavior, and plasma content. Method: We systematically investigated differences in tau P301S transgenic mice (PS19 line) and wildtype littermates of different sex behavioral performance, tau neuropathology, and biomarkers in plasma and brain. Results: Male P301S transgenic mice exhibited significant changes in weight loss, survival rate, clasping, kyphosis, composite phenotype assessment, nest building performance, tau phosphorylation at Ser202/Thr205, and astrocyte activation compared to that of wild-type littermates. In contrast, female P301S transgenic mice were only sensitive in the Morris water maze and open field test. In addition, we characterized the absence of macrophage-inflammatory protein (MIP-3α) and the upregulation of interferon (IFN)-γ, interleukin (IL)-5, and IL-6 in the plasma of P301S transgenic mice, which can be served as potential plasma biomarkers in P301S Tg mice. Male P301S transgenic mice expressed more monokine induced by IFN-γ (MIG), tumor necrosis factor-α (TNF-α), IL-10, and IL-13 than those of female P301S mice. Conclusion: Our findings highlight sexual dimorphism in the behavior, neuropathology, and plasma proteins in tau P301S transgenic AD mice, indicating that the use of male P301S transgenic mice may be more suitable for assessing anti-phosphorylated tau therapeutic strategies for AD and related tauopathies, and the MIP-3α may be a new potential plasma biomarker.

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  • Consistent levels of human tau expression across the lifespan of PS19 mice have been reported in plasma, whole brain, and brain subregions including brainstem and hippocampus.

    “Consistent levels of human tau expression across the lifespan of PS19 mice have also been reported in plasma, whole brain (Sun et al., 2020), and brain subregions including brainstem and hippocampus (Ono et al., 2022).”

    From Spontaneous pathology in PS19 tauopathy mice progresses via brain networks (2025) · cites this paper as Sun et al., 2020

    The Sun et al. citation is attached to plasma and whole-brain levels, not the brain-subregion claim cited to Ono et al. In Results, the paper reports that plasma human tau tended to increase from 3 to 8 months and stabilized only after 9 months; it also says human tau in total brain kept increasing from 3 to 12 months. Those findings contradict consistent levels across the observed ages. (LLM, conf=0.91)

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  • The variability observed in p-tau burden across the lifespan is consistent with earlier reports showing significant variability in spontaneous hippocampal p-tau accumulation in aged male and female PS19 mice.

    “The variability which we observed in p-tau burden across the lifespan is consistent with earlier reports showing significant variability in spontaneous hippocampal p-tau accumulation in aged male and female PS19 mice (Sun et al., 2020; Woerman et al., 2017).”

    From Spontaneous pathology in PS19 tauopathy mice progresses via brain networks (2025) · cites this paper as Sun et al., 2020

    The Results section (“Pathological tau development in P301S transgenic mice of different ages and sex”; page unavailable) reports age- and sex-related differences in hippocampal phosphorylated tau in P301S mice. It does not establish significant variability in spontaneous accumulation among aged mice within the male and female groups, as the citing sentence suggests. (LLM, conf=0.82)

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  • A related observation was reported recently in 3.5- to 12-month-old PS19 mice, showing a ~10% prolonged latency in the accelerating rotarod test.

    “A related observation was reported recently in 3.5- to 12-month-old PS19 mice, showing a ~10% prolonged latency in the accelerating rotarod test [29].”

    From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [29]

    The Results section ('P301S mice exhibited sex differences in coordination score system'; page unavailable) reports a 10% longer accelerating-rotarod fall latency in P301S transgenic mice than in wild-type mice. The Mice and Accelerating rotarod methods sections identify the PS19 line and describe monthly behavioral testing from 3 to 12 months, not the claimed 3.5-to-12-month age range. (LLM, conf=0.86)

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Authors
Sun, Y., Guo, Y., Feng, X., Jia, M., Ai, N., Dong, Y., Zheng, Y., Fu, L., Yu, B., Zhang, H., Wu, J., Yu, X., Wu, H., & Kong, W.
Affiliations
  • Jilin University (CN)
  • Jilin Agricultural University (CN)
Corresponding author
  • Wu, Hui
  • Kong, Wei
ORCID
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2020-02-24
Volume
17
Issue
1
Pages
72-72
ISSN
1742-2094 (ISSN-L)
DOI
10.1186/s12974-020-01749-w
PMC
PMC7041244
OpenAlex
W3012405369
Cited by
122
References
5
Citations by year
2026: 14 · 2025: 31 · 2024: 20 · 2023: 18 · 2022: 23 · 2021: 13 · 2020: 3
FWCI
8.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroinflammation (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Jilin Scientific and Technological Development Program (20190201185JC)
  • National Natural Science Foundation of China (31971142)
  • Fundamental Research Funds for the Central Universities (2019JCXK-55)
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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, sexual dimorphism, CCL20, plasma biomarkers, tau phosphorylation, astrocyte activation, neuroinflammation, interferon-gamma, interleukin-6, IL-5, behavioral phenotypes, sex differences in neurodegeneration
MeSH terms
Alzheimer Disease, Animals, Disease Models, Animal, Female, Humans, Male, Mice, Transgenic, Sex Characteristics, Biomarkers, tau Proteins, Mice, Chemokine CCL20

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