Estrogen activates Alzheimer's disease genes
Abstract Introduction Women are at increased risk for Alzheimer's disease (AD), but the reason why remains unknown. One hypothesis is that low estrogen levels at menopause increases vulnerability to AD, but this remains unproven. Methods We compared neuronal genes upregulated by estrogen in ova...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| Subjects: | |
| Online Access: | https://doi.org/10.1016/j.trci.2019.09.004 |
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| author | Abhirami Ratnakumar Samuel E. Zimmerman Bryen A. Jordan Jessica C. Mar |
| author_facet | Abhirami Ratnakumar Samuel E. Zimmerman Bryen A. Jordan Jessica C. Mar |
| author_sort | Abhirami Ratnakumar |
| collection | DOAJ |
| description | Abstract Introduction Women are at increased risk for Alzheimer's disease (AD), but the reason why remains unknown. One hypothesis is that low estrogen levels at menopause increases vulnerability to AD, but this remains unproven. Methods We compared neuronal genes upregulated by estrogen in ovariectomized female rhesus macaques with a database of >17,000 diverse gene sets and applied a rare variant burden test to exome sequencing data from 1208 female AD patients with the age of onset < 75 years and 2162 female AD controls. Results We found a striking overlap between genes upregulated by estrogen in macaques and genes downregulated in the human postmortem AD brain, and we found that estrogen upregulates the APOE gene and that progesterone acts antagonistically to estrogen genome‐wide. We also found that female patients with AD have excess rare mutations in the early menopause gene MCM8. Discussion We show with genomic data that the menopausal loss of estrogen could underlie the increased risk for AD in women. |
| format | Article |
| id | doaj-art-a7922dadae5046d7900a11babc4d41a6 |
| institution | OA Journals |
| issn | 2352-8737 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj-art-a7922dadae5046d7900a11babc4d41a62025-08-20T02:36:54ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372019-01-015190691710.1016/j.trci.2019.09.004Estrogen activates Alzheimer's disease genesAbhirami Ratnakumar0Samuel E. Zimmerman1Bryen A. Jordan2Jessica C. Mar3Department of Systems and Computational BiologyAlbert Einstein College of MedicineBronxNYUSADepartment of Systems and Computational BiologyAlbert Einstein College of MedicineBronxNYUSADominick P. Purpura Department of NeuroscienceAlbert Einstein College of MedicineBronxNYUSADepartment of Systems and Computational BiologyAlbert Einstein College of MedicineBronxNYUSAAbstract Introduction Women are at increased risk for Alzheimer's disease (AD), but the reason why remains unknown. One hypothesis is that low estrogen levels at menopause increases vulnerability to AD, but this remains unproven. Methods We compared neuronal genes upregulated by estrogen in ovariectomized female rhesus macaques with a database of >17,000 diverse gene sets and applied a rare variant burden test to exome sequencing data from 1208 female AD patients with the age of onset < 75 years and 2162 female AD controls. Results We found a striking overlap between genes upregulated by estrogen in macaques and genes downregulated in the human postmortem AD brain, and we found that estrogen upregulates the APOE gene and that progesterone acts antagonistically to estrogen genome‐wide. We also found that female patients with AD have excess rare mutations in the early menopause gene MCM8. Discussion We show with genomic data that the menopausal loss of estrogen could underlie the increased risk for AD in women.https://doi.org/10.1016/j.trci.2019.09.004EstrogenMenopauseMitochondriaAPOEMCM8ASPM |
| spellingShingle | Abhirami Ratnakumar Samuel E. Zimmerman Bryen A. Jordan Jessica C. Mar Estrogen activates Alzheimer's disease genes Alzheimer’s & Dementia: Translational Research & Clinical Interventions Estrogen Menopause Mitochondria APOE MCM8 ASPM |
| title | Estrogen activates Alzheimer's disease genes |
| title_full | Estrogen activates Alzheimer's disease genes |
| title_fullStr | Estrogen activates Alzheimer's disease genes |
| title_full_unstemmed | Estrogen activates Alzheimer's disease genes |
| title_short | Estrogen activates Alzheimer's disease genes |
| title_sort | estrogen activates alzheimer s disease genes |
| topic | Estrogen Menopause Mitochondria APOE MCM8 ASPM |
| url | https://doi.org/10.1016/j.trci.2019.09.004 |
| work_keys_str_mv | AT abhiramiratnakumar estrogenactivatesalzheimersdiseasegenes AT samuelezimmerman estrogenactivatesalzheimersdiseasegenes AT bryenajordan estrogenactivatesalzheimersdiseasegenes AT jessicacmar estrogenactivatesalzheimersdiseasegenes |