that GABA interneuron dysfunction is particularly severe in APOE4 carriers (Li et al., 2009); (3) the previously identified macrophage enriched metabolic network (MEMN) in peripheral tissues and strongly supported as causal for a number of metabolic and vascular traits related to obesity, diabetes and heart disease (Chen et al., 2008; Emilsson et al., 2008), is remarkably enriched within the brain immune/microglia module (3.9 fold, P= 2.4e-46). This is of interest given the strong epidemiological evidence for metabolic- and vascular-based exposure on LOAD (Huang and Mucke, 2012; Murray et al., 2011); (4) The postsynaptic density proteome in the human neo-cortex of 748 proteins over-represented with risk loci known to underlie cognitive, affective and motor phenotypes (Bayes et al., 2011), was significantly enriched in the synaptic transmission module (3 fold, P = 1.6e-32). It is still unclear how and which of these different biological processes mentioned above interact to affect LOAD, however it is likely that only few downstream mechanisms on which many diverse effects converge are causally related to LOAD (Huang and Mucke, 2012; Murray et al., 2011). The accumulated data show a strikingly coherent organization of molecular processes in the LOAD-associated network.
