Gene-by-region study design provides novel insights into AD. (a) Region (x-axis) and disease (y-axis) T-statistics for each gene (point) are plotted, along with the line of best fit. We find a significant correlation between disease and region. The number of these genes differentially expressed with both region and disease (four corners) are displayed in grey, with P-values representing the significance of enrichment (in dark grey) or depletion (in italics). Dashed lines correspond to significant differential expression (P < 0.05). (b) Representative genes for each gene-by-region pattern of expression. Box plots of gene expression levels (y-axis) are displayed for each of the four groups (x-axis): CA1 in control (C1), CA3 in control (C3), CA1 in AD (A1), and CA3 in AD (A3). (c) The four vulnerability genes show higher expression in CA1 than CA3 and also increase with AD to a larger degree in CA1 compared with CA3. Labeling as in (b). (d) The three protection genes show higher expression in CA3 than CA1 and also increase with AD to a larger degree or decrease with AD to a smaller degree in CA3 compared with CA1. Note that there are two significant probes for UNC13C. Labeling as in (b).