Analysis of differential gene expression in prefrontal cortex samples between non-demented individuals and AD patients revealed massive changes, with more than 18,000 transcripts significantly regulated (ANOVA p<1E–6) by more than 28% (see Fig. S1). Much of this differential expression was due to a single gene expression pattern that defined the first principal component (PC1) in both AD and normal samples. PC1 explained 45% of variance in the upregulated genes and 60% of variance in the downregulated genes. As shown on the heat map in Figure 1, AD and normal samples dominated the opposite ends of this gene expression pattern, with some subjects from each group in the intermediate range. When normal and AD subjects were considered separately, it was largely the same genes that contributed to the PC1 pattern in both AD and normal samples as shown by correlation analysis in Figure S1. This analysis indicated that the same major biological process reflected in the gene expression started in normal brains and continued developing in AD brains. We found a significant correlation of PC1 with chronological age in non-demented individuals
