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. 2023 May 1;55(5):1023–1032. doi: 10.1038/s12276-023-00993-3

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — a A functional enrichment analysis to reveal protein‒protein interaction networks (31 nodes). Five proteins (PPP2CB, NUP107, GAPDH, NPRL2, and NUP85) were used as predicted functional partners (PFP) in the network model. Three clusters were detected by K-means clustering analysis. Colored nodes: query proteins and first shell of interactors; white nodes: second shell of interactors; filled nodes: some three-dimensional structures known or predicted; edges: protein‒protein associations. b–e Enriched KEGG pathways and gene ontology analysis (BP, CC, MF) using glucose metabolic genes specifically regulated in women. The analytic threshold of enrichment analyses was an FDR-adjusted P < 0.05. f A functional enrichment analysis to reveal protein‒protein interaction networks with key AD-related biomarker genes (APP, BACE1, BACE2, and MAPT; amyloid- or tau-related genes) (36 nodes). Five proteins (PPP2CB, NUP107, GAPDH, NPRL2, and NUP85) were used as predicted functional partners (PFP) in the network model. Colored nodes: query proteins and first shell of interactors; white nodes: second shell of interactors; filled nodes: some three-dimensional structures known or predicted; edges: protein‒protein associations. g mRNA expression of genes directly linked with key AD genes. Two-way ANOVA with Tukey’s post hoc test (cutoff: P < 0.01). h ROC curve analysis using the ALDOA, ENO2, PRKACB, and PPP2R5D genes. The logistic regression analysis showed significant results for women but not men. i Graphical summary of this study. Padj FDR-adjusted P values, DEG differentially expressed genes, BP biological process, CC cellular components, MF molecular functions, PFP predicted functional partners.