Neuroendocrine signaling as a pathological seed for the female bias of Alzheimer's disease and the concept of estrobolome.
| Title: | Neuroendocrine signaling as a pathological seed for the female bias of Alzheimer's disease and the concept of estrobolome. |
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| Authors: | Rapaka D; Department of Pharmacy, DDT College of Medicine, Gaborone, Botswana. Electronic address: drapaka@ddtcollegeofmedicine.com.; Saniotis A; Department of Medical Microbiology, Cihan University-Erbil, Kurdistan Region, Erbil, Iraq.; Thatayaone M; School of Pharmacy, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana.; Bitra VR; School of Pharmacy, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana. Electronic address: bitrav@ub.ac.bw. |
| Source: | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2026 Feb; Vol. 195, pp. 118999. Date of Electronic Publication: 2026 Jan 12. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 8213295 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1950-6007 (Electronic) Linking ISSN: 07533322 NLM ISO Abbreviation: Biomed Pharmacother Subsets: MEDLINE |
| Imprint Name(s): | Publication: Paris : Editions Scientifiques Elsevier; Original Publication: New York, N.Y. : Masson Pub. USA, Inc., c1982- |
| MeSH Terms: | Alzheimer Disease*/epidemiology ; Alzheimer Disease*/metabolism ; Alzheimer Disease*/microbiology ; Alzheimer Disease*/physiopathology ; Alzheimer Disease*/pathology ; Gastrointestinal Microbiome*/physiology ; Estrogens*/metabolism ; Neurosecretory Systems*/metabolism; Brain/metabolism ; Brain/physiopathology ; Signal Transduction/physiology ; Humans ; Female ; Animals ; Risk Factors |
| Abstract: | The prevalence of Alzheimer's disease (AD) is anticipated to escalate with the global increase in life expectancy. Although sex-based differences in AD have been previously documented, doubts persist regarding the relationship between sex and pathophysiological pathways. Sex hormones may contribute to these disparities, with a heightened risk of AD-related dementia associated with oophorectomy before menopause. We cannot ascertain if estrogens alone are solely accountable for this accelerated pathological progression of the disease. Estrogens are regulated by the gut microbiota. Thus, the gut-estrogen-brain axis appears to be implicated as a potential new influencer in the pathophysiology of AD, as the female microbiome differs from the male gut microbiome. This suggests it could be a risk factor for the higher prevalence of AD in women. This review speculates on the possible mechanisms for AD prevalence in women, including both anatomical and neuroendocrinological perspectives.; (Copyright © 2026 The Authors. Published by Elsevier Masson SAS.. All rights reserved.) |
| Competing Interests: | Declaration of Competing Interest The authors declare no conflict of interest. |
| Contributed Indexing: | Keywords: Alzheimer’s disease; Blood-brain barrier; Estrobolome; Estrogen receptors; Gut-microbiome |
| Substance Nomenclature: | 0 (Estrogens) |
| Entry Date(s): | Date Created: 20260111 Date Completed: 20260205 Latest Revision: 20260205 |
| Update Code: | 20260206 |
| DOI: | 10.1016/j.biopha.2026.118999 |
| PMID: | 41520466 |
| Database: | MEDLINE |
Journal Article; Review