Extended Data Fig. 3: Sex-dependent neutrophil gene patterns during cognitive impairment.
a, Correlation of explanatory variables in dataset (Kendals Tau correlation) in subjects described in Fig. 2a,b (n = 94). b, Boxplot showing distribution of samples according to age for HC (n = 47), MCI (n = 38) and AD (n = 9). Boxplots showing MMSE (c) and QRDS (d) scores per patient according to clinical diagnosis HC (n = 47), MCI (n = 38) and AD (n = 9). One-way ANOVA. Data are shown using box-whisker plots (box, median and 25th to 75th percentile; whiskers; minimum to maximum). e, Volcano plot showing DEGs for comparisons between MCI (n = 39) and HC (n = 47) (top half), and AD (n = 9) vs MCI (n = 38) (bottom half). Likelihood Ratio Test with BH correction. (P < 0.05) f, Enriched pathways in APOE ε3/4 vs APOE ε3/3 carriers according to clinical diagnosis and sex (HC:F:33, n = 12; HC:F:34 n = 13, HC:M:33, n = 13; HC:M:34 n = 14. fGSEA permutation-based test. (*P < 0.05) g, DEGs heatmap of male HC and MCI patients carrying APOE ε3/3 and APOE ε3/4 genotypes. Male HC APOE ε3/3 (n = 12), Male HC APOE ε3/4 (n = 12), Male MCI APOE ε3/3 (n = 9), Male MCI APOE ε3/4 (n = 8). h, Volcano plots of DEGs comparing male MCI vs HC neutrophils in APOE ε3/4 carriers. Likelihood Ratio Test with BH correction. i, IPA comparison analysis of MCI vs HC male samples in APOE ε3/3 and APOE ε3/4 carriers (P < 0.05). One-sided Fisher′s Exact test with BH corrections (h,i). j, Upstream regulators identified using IPA, enriched in APOE ε3/4 male carriers according to HC and MCI diagnosis. k, Custom pathway enrichment score for DEGs comparing CI vs HC patients, described in Fig. 2a, b, according to mature neutrophil marker gene list from public snRNA-seq dataset by Schulte-Schrepping et al.22. HC (n = 47), CI (n = 47), Padj < 0.05. Permutation-based test with BH correction. l, PCA of whole blood RNA-seq data from MCSA dataset and cell type prediction. m, Deconvolution of MCSA samples according to immune cell type (n = 422). n, Pathway enrichment analysis of DEGs in HC females APOE ε3/4 vs APOE ε3/3 (n = 72) and males (n = 78), and comparison of MCI vs HC samples in APOE ε3/3 males (n = 54) and females (n = 61).
