Fig. 4

Proteins involved in multiple pathways are altered in AD and by APOE genotype and brain region. Using Ingenuity Pathway analysis to investigate pathway alterations in the 1532 proteins that were changed more than 20% in the most vulnerable brain condition (APOE3/4 BA41/42) shows that in AD there is a clear upregulation of pathways involved in the immune response and cellular signaling and down regulation of several pathways involved in synaptic function including long term potentiation, glutamate signaling, and calcium ignaling. These pathways were differentially regulated in the different brain regions and APOE genotypes. Comparing APOE4 to APOE3 carriers within the control (con) and AD groups similarly reveals region-specific effects of APOE isoform on the synaptic proteome. Z-scores are plotted in d with upregulated proteins shown in red and downregulated in green