Fig. 2

Pronounced sexual dimorphism of immune signaling, glial markers, and molecular markers of pathology in 3xTg-AD mice. A) Principal component analysis of combined protein data across only sham-injured animals (left) and all samples (injured and sham-injured, right), reveals strong separation between male and female mice on the first two PCs. Female replicate samples measured in male batch assays are shown in purple, emphasizing that the effects of sex were biological, rather than technical. Percent variance described by each PC is annotated in parentheses. B) Sham-injured control mice show distinct baseline sex differences in expression of glial markers, pathological markers, MAPK signaling, and cytokines. Proteins are categorized by function, then clustered by Euclidean distance within each category. Red to blue indicates relatively high to low expression among all sham-injured animals (n = 13 males, n = 10 females, z-scored). Of the 46 measured immune and pathological marker proteins in sham-injured animals, 37 from the frontal cortex (80%) and 30 from the hippocampus (65%) had higher average expression in males compared to females. C) Pie charts for each region and sample set. Left: just sham-injured. Right: all samples, injured and sham-injured show high proportions of all analytes measured (4 glial markers, 4 pathological markers, 9 MAPK, 30 cytokines) that are significantly elevated (p < 0.05, Wilcoxon rank-sum) in males (blue) or females (pink). See summary of significant differences in Table S3