Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged rats
Summary Female sex and Apolipoprotein (APOE) ε4 genotype are top risk factors for late-onset Alzheimer’s disease. This research investigates how these two risk factors might interact to influence biomarkers of brain health at middle age using a rat model. Compared to healthy controls, male rats with...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | Biology of Sex Differences |
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| Online Access: | https://doi.org/10.1186/s13293-025-00694-8 |
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| author | Bonnie H. Lee Melike Cevizci Stephanie E. Lieblich Liisa A. M. Galea |
| author_facet | Bonnie H. Lee Melike Cevizci Stephanie E. Lieblich Liisa A. M. Galea |
| author_sort | Bonnie H. Lee |
| collection | DOAJ |
| description | Summary Female sex and Apolipoprotein (APOE) ε4 genotype are top risk factors for late-onset Alzheimer’s disease. This research investigates how these two risk factors might interact to influence biomarkers of brain health at middle age using a rat model. Compared to healthy controls, male rats with hAPOEε4 genotype showed reduced neural stem cell-like cells and new adult-born brain cells and increased microglia (marker of inflammation in the brain) at middle age. In contrast, female rats with hAPOEε4 genotype showed increased new adult-born neurons, but no changes in the other cell types, suggesting a possible compensatory response to the effects of hAPOEε4 at this time point. These results highlight the importance of examining sex-specific pathways in AD, as they may uncover unique protective mechanisms and inform development of tailored treatment strategies. |
| format | Article |
| id | doaj-art-74b1281aabce4b52bd2b6ab121f35818 |
| institution | Kabale University |
| issn | 2042-6410 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology of Sex Differences |
| spelling | doaj-art-74b1281aabce4b52bd2b6ab121f358182025-02-09T12:04:55ZengBMCBiology of Sex Differences2042-64102025-02-0116111410.1186/s13293-025-00694-8Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged ratsBonnie H. Lee0Melike Cevizci1Stephanie E. Lieblich2Liisa A. M. Galea3Graduate Program in Neuroscience, University of British ColumbiaDjavad Mowafaghian Centre for Brain Health, University of British ColumbiaDjavad Mowafaghian Centre for Brain Health, University of British ColumbiaGraduate Program in Neuroscience, University of British ColumbiaSummary Female sex and Apolipoprotein (APOE) ε4 genotype are top risk factors for late-onset Alzheimer’s disease. This research investigates how these two risk factors might interact to influence biomarkers of brain health at middle age using a rat model. Compared to healthy controls, male rats with hAPOEε4 genotype showed reduced neural stem cell-like cells and new adult-born brain cells and increased microglia (marker of inflammation in the brain) at middle age. In contrast, female rats with hAPOEε4 genotype showed increased new adult-born neurons, but no changes in the other cell types, suggesting a possible compensatory response to the effects of hAPOEε4 at this time point. These results highlight the importance of examining sex-specific pathways in AD, as they may uncover unique protective mechanisms and inform development of tailored treatment strategies.https://doi.org/10.1186/s13293-025-00694-8Sex differencesAlzheimer’s diseaseHippocampusMicrogliaMaleFemale |
| spellingShingle | Bonnie H. Lee Melike Cevizci Stephanie E. Lieblich Liisa A. M. Galea Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged rats Biology of Sex Differences Sex differences Alzheimer’s disease Hippocampus Microglia Male Female |
| title | Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged rats |
| title_full | Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged rats |
| title_fullStr | Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged rats |
| title_full_unstemmed | Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged rats |
| title_short | Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged rats |
| title_sort | sex specific influences of apoeε4 genotype on hippocampal neurogenesis and progenitor cells in middle aged rats |
| topic | Sex differences Alzheimer’s disease Hippocampus Microglia Male Female |
| url | https://doi.org/10.1186/s13293-025-00694-8 |
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