Premenstrual dysphoric disorder as a potential predisposing factor for Alzheimer’s disease: a review

TL;DR

This paper reviews how premenstrual dysphoric disorder might be linked to Alzheimer’s disease through shared biological mechanisms, suggesting it could help identify women at higher risk.

Contribution

The paper introduces a novel perspective linking PMDD and AD via shared neuroendocrine and molecular pathways.

Findings

PMDD and AD may share biological pathways involving estradiol and allopregnanolone.

Dysregulation of GABAergic and serotonergic systems may connect PMDD and AD.

APOE ϵ4 allele and sex-specific vulnerabilities are highlighted as potential links.

Abstract

Premenstrual dysphoric disorder (PMDD) and Alzheimer’s disease (AD) differ significantly in terms of onset period and clinical manifestations. However, recent studies suggest that the two conditions may share potential links at the neuroendocrine and molecular levels. This review synthesizes current research progress and explores the intersecting biological pathways between PMDD and AD, with a particular focus on dynamic fluctuations in estradiol (E2) and allopregnanolone (ALLO), dysregulation of the γ-aminobutyric acid (GABA)ergic system and serotonergic (5-HT) neurotransmitter systems, and sex-specific vulnerability associated with the apolipoprotein E epsilon 4 (APOE ϵ4) allele. These mechanisms suggest that PMDD may serve as a potential biological precursor state for AD, offering valuable implications for early screening and intervention. The analysis provides new theoretical insights and research directions for identifying high-risk female populations, understanding sex differences in AD pathogenesis, and developing targeted therapeutic strategies.

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