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Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study
OBJECTIVE: Women have a higher lifetime risk of Alzheimer's disease (AD) than men. Among cognitively normal (CN) older adults, women exhibit elevated tau positron emission tomography (PET) signal compared with men. We explored whether menopause exacerbates sex differences in tau deposition in m...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233144/ https://www.ncbi.nlm.nih.gov/pubmed/35471588 http://dx.doi.org/10.1002/ana.26382 |
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author | Buckley, Rachel F. O'Donnell, Adrienne McGrath, Emer R. Jacobs, Heidi I.L. Lois, Cristina Satizabal, Claudia L. Ghosh, Saptaparni Rubinstein, Zoe B. Murabito, Joanne M. Sperling, Reisa A. Johnson, Keith A. Seshadri, Sudha Beiser, Alexandra S. |
author_facet | Buckley, Rachel F. O'Donnell, Adrienne McGrath, Emer R. Jacobs, Heidi I.L. Lois, Cristina Satizabal, Claudia L. Ghosh, Saptaparni Rubinstein, Zoe B. Murabito, Joanne M. Sperling, Reisa A. Johnson, Keith A. Seshadri, Sudha Beiser, Alexandra S. |
author_sort | Buckley, Rachel F. |
collection | PubMed |
description | OBJECTIVE: Women have a higher lifetime risk of Alzheimer's disease (AD) than men. Among cognitively normal (CN) older adults, women exhibit elevated tau positron emission tomography (PET) signal compared with men. We explored whether menopause exacerbates sex differences in tau deposition in middle‐aged adults. METHODS: 328 CN participants from the Framingham Study (mean age = 57 years (±10 years), 161 women, of whom, 104 were post‐menopausal) underwent tau and β‐amyloid (Aβ)‐PET neuroimaging. We examined global Aβ‐PET, and tau‐PET signal in 5 regions identified a priori as demonstrating significant sex differences in older adults (in temporal, inferior parietal, middle frontal, and lateral occipital regions). We examined sex and menopause status‐related differences in each region‐of‐interest, using linear regressions, as well as interactions with Aβ and APOEε4 genotype. RESULTS: Women exhibited higher tau‐PET signal (p < 0.002), and global Aβ‐PET (p = 0.010), than men in inferior parietal, rostral middle frontal, and lateral occipital regions. Compared with age‐matched men, post‐menopausal women showed significantly higher tau‐PET signal in parieto‐occipital regions (p < 0.0001). By contrast, no differences in tau‐PET signal existed between pre‐menopausal women and men. Aβ‐PET was not associated with menopausal status or age. Neither Aβ‐PET nor APOEε4 status moderated sex or menopause associations with tau‐PET. INTERPRETATION: Clear divergence in tauopathy between the sexes are apparent approximately 20 years earlier than previously reported. Menopause status moderated sex differences in Aβ and tau‐PET burden, with tau first appearing post‐menopause. Sex and menopause differences consistently appeared in middle frontal and parieto‐occipital regions but were not moderated by Aβ burden or APOEε4, suggesting that menopause‐related tau vulnerability may be independent of AD‐related pathways. ANN NEUROL 2022;92:11–22 |
format | Online Article Text |
id | pubmed-9233144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92331442022-10-14 Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study Buckley, Rachel F. O'Donnell, Adrienne McGrath, Emer R. Jacobs, Heidi I.L. Lois, Cristina Satizabal, Claudia L. Ghosh, Saptaparni Rubinstein, Zoe B. Murabito, Joanne M. Sperling, Reisa A. Johnson, Keith A. Seshadri, Sudha Beiser, Alexandra S. Ann Neurol Research Articles OBJECTIVE: Women have a higher lifetime risk of Alzheimer's disease (AD) than men. Among cognitively normal (CN) older adults, women exhibit elevated tau positron emission tomography (PET) signal compared with men. We explored whether menopause exacerbates sex differences in tau deposition in middle‐aged adults. METHODS: 328 CN participants from the Framingham Study (mean age = 57 years (±10 years), 161 women, of whom, 104 were post‐menopausal) underwent tau and β‐amyloid (Aβ)‐PET neuroimaging. We examined global Aβ‐PET, and tau‐PET signal in 5 regions identified a priori as demonstrating significant sex differences in older adults (in temporal, inferior parietal, middle frontal, and lateral occipital regions). We examined sex and menopause status‐related differences in each region‐of‐interest, using linear regressions, as well as interactions with Aβ and APOEε4 genotype. RESULTS: Women exhibited higher tau‐PET signal (p < 0.002), and global Aβ‐PET (p = 0.010), than men in inferior parietal, rostral middle frontal, and lateral occipital regions. Compared with age‐matched men, post‐menopausal women showed significantly higher tau‐PET signal in parieto‐occipital regions (p < 0.0001). By contrast, no differences in tau‐PET signal existed between pre‐menopausal women and men. Aβ‐PET was not associated with menopausal status or age. Neither Aβ‐PET nor APOEε4 status moderated sex or menopause associations with tau‐PET. INTERPRETATION: Clear divergence in tauopathy between the sexes are apparent approximately 20 years earlier than previously reported. Menopause status moderated sex differences in Aβ and tau‐PET burden, with tau first appearing post‐menopause. Sex and menopause differences consistently appeared in middle frontal and parieto‐occipital regions but were not moderated by Aβ burden or APOEε4, suggesting that menopause‐related tau vulnerability may be independent of AD‐related pathways. ANN NEUROL 2022;92:11–22 John Wiley & Sons, Inc. 2022-05-17 2022-07 /pmc/articles/PMC9233144/ /pubmed/35471588 http://dx.doi.org/10.1002/ana.26382 Text en © 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Buckley, Rachel F. O'Donnell, Adrienne McGrath, Emer R. Jacobs, Heidi I.L. Lois, Cristina Satizabal, Claudia L. Ghosh, Saptaparni Rubinstein, Zoe B. Murabito, Joanne M. Sperling, Reisa A. Johnson, Keith A. Seshadri, Sudha Beiser, Alexandra S. Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study |
title | Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study |
title_full | Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study |
title_fullStr | Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study |
title_full_unstemmed | Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study |
title_short | Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study |
title_sort | menopause status moderates sex differences in tau burden: a framingham pet study |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233144/ https://www.ncbi.nlm.nih.gov/pubmed/35471588 http://dx.doi.org/10.1002/ana.26382 |
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