Figure 1.

Cluster analysis of transcript patterns. (a–d) An unsupervised cluster analysis of transcript profiles yielded four patterns. Use of z-scores controlled for effects of absolute levels of signal. (a) Cluster 1 was modal and involved upregulation of the transcript in APOE4 BA 21 temporal cortex and downregulation in APOE4 BA 1/2/3 primary somatosensory cortex; expression levels in these two regions were not strikingly different in the APOE3 group. (b–c) The next most frequent pattern involved upregulation of expression in primary somatosensory cortex of the APOE4 group, with downregulation in the temporal cortex; differences between these regions in the E3 group were relatively smaller. (d) This pattern was least frequent. (e) CASP6, an example of a transcript included in cluster1. CASP6 is involved in programmed cell death. It is strongly upregulated in the temporal cortex of the APOE4 group, while modestly downregulated in the primary somatosensory cortex of the APOE4 group. This may represent a response in the APOE4 group that confers susceptibility to AD pathology. (f) FKBPL, an example of a transcript from cluster 2. FKBPL is an immunophilin that has neuroprotective properties. It was strongly upregulated in BA 1/2/3 (primary somatosensory cortex) of the APOE4 group and modestly downregulated in BA 21 (temporal cortex) of the APOE3 group, reflecting a possible neuroprotective response in BA 1/2/3. Units on the y axis represent expression in signal intensity units. Along the x axis are temporal and parietal variables, as a function of APOE group.