Single‐cell transcriptomic analysis reveals APOE genotype‐dependent sex differences in Alzheimer's disease
Year: 2026
Type: article
Abstract: INTRODUCTION: Alzheimer's disease (AD) is the most common form of dementia, with approximately two-thirds of AD patients being female. Basic and clinical research studies provide strong evidence that sex-specific differences contribute to AD complexity. Additionally, sex-specific interactions between apolipoprotein E (APOE) 𝜀4, the primary genetic risk factor of AD, and AD-associated neurodegenerative processes are well documented. However, there has been no comprehensive investigation into the interplay between sex and APOE genotypes at the single-cell level. METHODS: In this study, we systematically explore sex- and APOE-associated differences in single-cell transcriptomics in AD. RESULTS: Our work provides a high-resolution landscape of sex and APOE genotype-specific transcriptomic changes across 54 high-resolution cell types in AD and highlights genes and brain cell populations that show significant sex- and APOE-specific differences in AD. DISCUSSION: This study lays the groundwork for understanding the complex molecular mechanisms of AD and informs the development of targeted sex- and APOE-stratified interventions for AD.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.71463
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
Awards: Integrative Network Modeling of Cognitive Resilience to Alzheimer's Disease, Integrative Network Biology Approaches to Identify, Characterize and Validate Molecular Subtypes in Alzheimer's Disease, Molecular Characterization and Validation of Gender Differences in Alzheimers Disease Pathogenesis, Systematic dissection of novel Alzheimer's genes in microglia, Dissect regulation of glial nets surrounding amyloid plaques in Alzheimer's disease, Big Omics Data Engine 2 Supercomputer, Towards a comprehensive signaling pathway map of parahippocampal vulnerability in Alzheimers Disease, Dissect the interplay between sex and APOE at the single cell level to uncover novel pathways, targets and therapeutics for Alzheimer's disease, Systematic identification of genetic modifiers of dysfunctional neuronal networks in Alzheimer's disease, Characterization of protective roles of ApoE2 against aging and Alzheimer's disease, COVID and Translational Science supercomputer (CATS), Dissect the interplay between sex and APOE at the single cell level to uncover novel pathways, targets and therapeutics for Alzheimer's disease, Conduits: Mount Sinai Health System Translational Science Hub
OpenAlex ID: W7160769382