Fig. 5: Stain-specific load correlations with RNAseq gene expression to identify genes impacted by changes in load within the hippocampal formation.

a Gene expression by load Pearson R correlation coefficients and p-value relationships without age adjustment for each stain. Significantly correlated genes (uncorrected p-value < 0.05) are colored in each plot. The percentage of uncorrected significant genes is indicated within the plot. The top five positive and negative FDR significant (FDR p-value < 0.05) correlated genes are labeled. b Gene expression by load Pearson R correlation coefficients and p-value relationships after age adjustment for each stain. Significantly correlated genes (uncorrected p-value < 0.05) are colored according to stain. The percentage of uncorrected significant genes is indicated within the plot. The top five positive and negative FDR significant (FDR p-value < 0.05) correlated genes are labeled. c Comparison of Pearson R correlation coefficients without and with age adjustment per stain. Gene correlations that were exclusively significant (uncorrected-p-value < 0.05) without age adjustment are considered age-dependent (orange). Gene correlations that were exclusively significant (uncorrected-p-value < 0.05) with age adjustment are considered age-independent (blue). The specific influence of age and load cannot be disseminated in gene correlations that were significant (uncorrected-p-value < 0.05) under both correlation conditions (green). All nonsignificant (uncorrected-p-value < 0.05) genes are labeled in gray. The percentage of significant genes per category is represented in the bottom right corner. The top 3 most significant genes per correlation method category are labeled per stain plot (FDR p-value < 0.05). d Individual relationship between gene expression and load with age for the top age-dependent and independently correlated genes with Iba1. i. Galnt6 was exclusively significantly correlated with Iba1 without age adjustment. An increase in Iba1 load and Galnt6 expression occurs between 6 m and 14 m. A positive relationship between Iba1 load and Galnt6 expression exists across both age groups as well as within each age group. ii. Tmem39a was exclusively significantly correlated with Iba1 after age adjustment. An increase in Iba1 load but not in Tmem39a expression occurs between 6 m and 14 m. A weak relationship between Iba1 load and Tmem39a expression exists across both age groups, but separate age-specific correlations with load and gene expression exist. 5XFAD mice only, 6 m: n = 17 mice, 14 m: n = 20 mice.