connection of the immune/microglia module to Huntington disease (HD), another neurodegenerative disease. HD pathology, caused by expanded alleles of a variable stretch of trinucleotide (CAG) repeat length in HTT (The Huntington’s Disease Collaborative Research Group, 1993), features astrogliosis and neurodegeneration of the striatum, prefrontal cortex and hippocampus. We constructed molecular networks in the PFC from 194 HD patients genotyped for CAG allele size (see Extended Experimental Procedures) and found that the PFC version of the immune/microglia module was well conserved between LOAD and HD in terms of gene annotation (75% overlap, P-value <1e-300). This module, however, did not show any alteration in connectivity in HD brains compared to the disease-free controls used in our LOAD study. Moreover, through a PCA we did not detect any gene expression correlation of the HD brain immune/microglia module to expanded CAG repeat length (r=-0.05, FDR=56%), a key biomarker for predicting HD severity (Gusella and MacDonald, 2006). Thus based on the comparison to HD, the disease-related effect of the immune/microglia module appears to be specific to LOAD (and possibly Nasu-Hakola disease).
