[en] INTRODUCTION: Alzheimer's disease (AD) shows significant sex differences in prevalence and clinical manifestations, but the underlying molecular mechanisms remain unclear.
METHODS: This study uses a large-scale single-cell transcriptomic atlas of the human prefrontal cortex to investigate sex-dependent molecular changes in AD. Our approach combined cell type-specific and sex-specific differential gene expression analysis, pathway enrichment, gene regulatory network construction and cell-cell communication analysis to identify sex-dependent changes.
RESULTS: We found significant sex-specific gene expression patterns and pathway alterations in AD. Male astrocytes showed changes in cell death pathways, with RPTOR as a key regulator, while female astrocytes had alterations in Wnt signaling and cell cycle regulation. Cell-cell communication analysis uncovered sex-specific intercellular signaling patterns, with male-specific impacts on apoptosis-related signaling and female-specific alterations in Wnt and calcium signaling.
DISCUSSION: This study reveals sex-dependent gene expression patterns, pathway alterations, and intercellular communication changes, suggesting the need for sex-specific approaches in AD research.
Centre de recherche :
Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group)
Disciplines :
Neurologie Sciences de la santé humaine: Multidisciplinaire, généralités & autres Biotechnologie Sciences du vivant: Multidisciplinaire, généralités & autres
Auteur, co-auteur :
Mohamed, Soudy
Sophie Le Bars
GLAAB, Enrico ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Biomedical Data Science
Co-auteurs externes :
no
Langue du document :
Anglais
Titre :
Sex-Dependent Molecular Landscape of Alzheimer's Disease Revealed by Large-Scale Single-Cell Transcriptomics
Date de publication/diffusion :
2024
Titre du périodique :
Alzheimer's and Dementia: the Journal of the Alzheimer's Association
ISSN :
1552-5260
eISSN :
1552-5279
Maison d'édition :
John Wiley & Sons, Hoboken, Etats-Unis - New Jersey
Peer reviewed :
Peer reviewed vérifié par ORBi
Focus Area :
Systems Biomedicine
Objectif de développement durable (ODD) :
3. Bonne santé et bien-être
Projet FnR :
FNR17104370 - Rebalancing Sleep-wake Disturbances In Parkinson's Disease With Deep Brain Stimulation, 2022 (01/06/2023-31/05/2026) - Enrico Glaab FNR17027921 - Predictive Biomarkers In Dystonia: Defining The Paradigm Of Monogenic Dystonia To Implement The Diagnosis And Prognosis Of Undiagnosed Forms, 2022 (01/06/2023-...) - Enrico Glaab U-AGR-7375 - INTER/JPND23/17999421/AD-PLCG2 - GLAAB Enrico
