CNS cell-type specific gene signatures, from the Allen Brain Atlas (http://www.brain-map.org/) were enriched in distinct network modules as previously observed (Oldham et al., 2008): neurons in the synaptic transmission modules (11 fold, P=3.7e-24), astrocytes in GABA biosynthesis module (22 fold, P=1.5e-15), oligodendrocytes in the nerve myelination module (30 fold, P=2.5e-30), choroid plexus cell types in the extracellular matrix module (35 fold, P=3.9e-15) and microglia signatures responding to amyloid-β treatment (Walker et al., 2006) in the immune module (10 fold, P=4.5e-20) (Figure 3C). In contrast to the GOC and LOC modules, conserved modules were not enriched for any CNS specific cell types (Figure 3C). Pathways enriched in the brain modules and not previously implicated in LOAD, may therefore represent novel disease mechanisms including, for instance, the glucuronosyl transferase activity and the dynein complex (Figure 3C). Moreover, the comprehensive representation of gene-gene interactions in the LOAD-associated networks can uncover novel gene members in pathways already implicated in LOAD, thus allowing us to work out a known pathologic mechanism in more detail than ever before. In summary, the immune module shows the statistically
