the overall cohort of LOAD and non-demented brains the mean±SD for sample PMI, pH and RIN were 17.8±8.3, 6.4±0.3 and 6.8±0.8, respectively. Extensive analysis of the effect of covariates on gene expression variation in LOAD and non-demented brains was carried out, as shown in Figure S1 and described in the Extended Experimental Procedures. Here, we used a robust linear regression model for covariate corrections in all our gene expression analyses (Experimental Procedures). Results of traditional differential expression analysis demonstrate that subsets of genes were up- or down-regulated in LOAD (Figure 2A). Consistent with the known progression and regional severity of LOAD pathology (Braak and Braak, 1991), we observed the PFC region contained the greatest number of differentially expressed genes (Figure 2B). Figure 2C summarizes the clustering or co-linearity of the various LOAD pathology traits and age within the HBTRC cohort, resulting in distinct groups of clinical pathology and age as separate clusters. For instance, the number of significant correlations of expression traits to neuropathology like Braak stage within the LOAD patient group was highest in the PFC region (Figure 2D). Given these observations and the fact that PFC is more commonly affected in LOAD than CB and VC (Braak and
