APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease mice
Abstract The most significant genetic risk factor for developing late-onset Alzheimer’s disease (AD) is the ε4 allele of apolipoprotein E (APOE4). APOE genotype and biological sex are key modulators of microglial and astroglial function, which exert multiple effects on AD pathogenesis. Here, we show...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-022-02650-4 |
| _version_ | 1811190402477195264 |
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| author | T. L. Stephen B. Breningstall S. Suresh C. J. McGill C. J. Pike |
| author_facet | T. L. Stephen B. Breningstall S. Suresh C. J. McGill C. J. Pike |
| author_sort | T. L. Stephen |
| collection | DOAJ |
| description | Abstract The most significant genetic risk factor for developing late-onset Alzheimer’s disease (AD) is the ε4 allele of apolipoprotein E (APOE4). APOE genotype and biological sex are key modulators of microglial and astroglial function, which exert multiple effects on AD pathogenesis. Here, we show astroglial interactions with amyloid plaques in the EFAD transgenic mouse model of AD. Using confocal microscopy, we observed significantly lower levels of astrocytic plaque coverage and plaque compaction (beneficial effects of glial barrier formation) with APOE4 genotype and female sex. Conversely, neurite damage and astrocyte activation in the plaque environment were significantly higher in APOE4 carriers and female mice. Astrocyte coverage of plaques was highest in APOE3 males and poorest in APOE4 females. Collectively, our findings provide new insights into the roles of astroglia and highlight the importance of addressing independent and interactive effects of APOE genotype and biological sex in understanding processes contributing to AD pathogenesis. |
| first_indexed | 2024-04-11T14:50:03Z |
| format | Article |
| id | doaj.art-8d6c4e8cfdff42199c50168849c16ea9 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-11T14:50:03Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-8d6c4e8cfdff42199c50168849c16ea92022-12-22T04:17:31ZengBMCJournal of Neuroinflammation1742-20942022-12-011911710.1186/s12974-022-02650-4APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease miceT. L. Stephen0B. Breningstall1S. Suresh2C. J. McGill3C. J. Pike4Leonard Davis School of Gerontology, University of Southern CaliforniaLeonard Davis School of Gerontology, University of Southern CaliforniaLeonard Davis School of Gerontology, University of Southern CaliforniaLeonard Davis School of Gerontology, University of Southern CaliforniaLeonard Davis School of Gerontology, University of Southern CaliforniaAbstract The most significant genetic risk factor for developing late-onset Alzheimer’s disease (AD) is the ε4 allele of apolipoprotein E (APOE4). APOE genotype and biological sex are key modulators of microglial and astroglial function, which exert multiple effects on AD pathogenesis. Here, we show astroglial interactions with amyloid plaques in the EFAD transgenic mouse model of AD. Using confocal microscopy, we observed significantly lower levels of astrocytic plaque coverage and plaque compaction (beneficial effects of glial barrier formation) with APOE4 genotype and female sex. Conversely, neurite damage and astrocyte activation in the plaque environment were significantly higher in APOE4 carriers and female mice. Astrocyte coverage of plaques was highest in APOE3 males and poorest in APOE4 females. Collectively, our findings provide new insights into the roles of astroglia and highlight the importance of addressing independent and interactive effects of APOE genotype and biological sex in understanding processes contributing to AD pathogenesis.https://doi.org/10.1186/s12974-022-02650-4Alzheimer’s diseaseApolipoprotein EAstrocytesGlial interactionsSex |
| spellingShingle | T. L. Stephen B. Breningstall S. Suresh C. J. McGill C. J. Pike APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease mice Journal of Neuroinflammation Alzheimer’s disease Apolipoprotein E Astrocytes Glial interactions Sex |
| title | APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease mice |
| title_full | APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease mice |
| title_fullStr | APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease mice |
| title_full_unstemmed | APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease mice |
| title_short | APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease mice |
| title_sort | apoe genotype and biological sex regulate astroglial interactions with amyloid plaques in alzheimer s disease mice |
| topic | Alzheimer’s disease Apolipoprotein E Astrocytes Glial interactions Sex |
| url | https://doi.org/10.1186/s12974-022-02650-4 |
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