Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition
Name:
s41598-021-90084-y.pdf
Size:
2.342Mb
Format:
PDF
Description:
Final Published Version
Author
Mosconi, L.Berti, V.
Dyke, J.
Schelbaum, E.
Jett, S.
Loughlin, L.
Jang, G.
Rahman, A.
Hristov, H.
Pahlajani, S.
Andrews, R.
Matthews, D.
Etingin, O.
Ganzer, C.
de Leon, M.
Isaacson, R.
Brinton, R.D.
Affiliation
Departments of Pharmacology and Neurology, College of Medicine, University of ArizonaIssue Date
2021
Metadata
Show full item recordPublisher
Nature ResearchCitation
Mosconi, L., Berti, V., Dyke, J., Schelbaum, E., Jett, S., Loughlin, L., Jang, G., Rahman, A., Hristov, H., Pahlajani, S., Andrews, R., Matthews, D., Etingin, O., Ganzer, C., de Leon, M., Isaacson, R., & Brinton, R. D. (2021). Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition. Scientific Reports, 11(1).Journal
Scientific ReportsRights
Copyright © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
All women undergo the menopause transition (MT), a neuro-endocrinological process that impacts aging trajectories of multiple organ systems including brain. The MT occurs over time and is characterized by clinically defined stages with specific neurological symptoms. Yet, little is known of how this process impacts the human brain. This multi-modality neuroimaging study indicates substantial differences in brain structure, connectivity, and energy metabolism across MT stages (pre-menopause, peri-menopause, and post-menopause). These effects involved brain regions subserving higher-order cognitive processes and were specific to menopausal endocrine aging rather than chronological aging, as determined by comparison to age-matched males. Brain biomarkers largely stabilized post-menopause, and gray matter volume (GMV) recovered in key brain regions for cognitive aging. Notably, GMV recovery and in vivo brain mitochondria ATP production correlated with preservation of cognitive performance post-menopause, suggesting adaptive compensatory processes. In parallel to the adaptive process, amyloid-β deposition was more pronounced in peri-menopausal and post-menopausal women carrying apolipoprotein E-4 (APOE-4) genotype, the major genetic risk factor for late-onset Alzheimer’s disease, relative to genotype-matched males. These data show that human menopause is a dynamic neurological transition that significantly impacts brain structure, connectivity, and metabolic profile during midlife endocrine aging of the female brain. © 2021, The Author(s).Note
Open access journalISSN
2045-2322PubMed ID
34108509Version
Final published versionae974a485f413a2113503eed53cd6c53
10.1038/s41598-021-90084-y
Scopus Count
Collections
Except where otherwise noted, this item's license is described as Copyright © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License.
Related articles
- Perimenopause and emergence of an Alzheimer's bioenergetic phenotype in brain and periphery.
- Authors: Mosconi L, Berti V, Quinn C, McHugh P, Petrongolo G, Osorio RS, Connaughty C, Pupi A, Vallabhajosula S, Isaacson RS, de Leon MJ, Swerdlow RH, Brinton RD
- Issue date: 2017
- A tale of two systems: Lessons learned from female mid-life aging with implications for Alzheimer's prevention & treatment.
- Authors: Mishra A, Wang Y, Yin F, Vitali F, Rodgers KE, Soto M, Mosconi L, Wang T, Brinton RD
- Issue date: 2022 Feb
- Evidence in support of chromosomal sex influencing plasma based metabolome vs APOE genotype influencing brain metabolome profile in humanized APOE male and female mice.
- Authors: Shang Y, Mishra A, Wang T, Wang Y, Desai M, Chen S, Mao Z, Do L, Bernstein AS, Trouard TP, Brinton RD
- Issue date: 2020
- Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging.
- Authors: Mosconi L, Berti V, Quinn C, McHugh P, Petrongolo G, Varsavsky I, Osorio RS, Pupi A, Vallabhajosula S, Isaacson RS, de Leon MJ, Brinton RD
- Issue date: 2017 Sep 26
- Regional patterns of gray matter volume, hypometabolism, and beta-amyloid in groups at risk of Alzheimer's disease.
- Authors: Wirth M, Bejanin A, La Joie R, Arenaza-Urquijo EM, Gonneaud J, Landeau B, Perrotin A, Mézenge F, de La Sayette V, Desgranges B, Chételat G
- Issue date: 2018 Mar