P = 5.1e-05) in an independent multi-center cohorts study (see Extended Experimental Procedures and Figure S4B). Additionally, we observed a progression of TYROBP expression changes across mild cognitive impairment (MCI) in the replication study (Figure S4B). Estimating what constitutes a “large” or “small” change in gene expression levels is challenging in microarray analyses. We note, however, that TYROBP was the 124th most differentially-expressed probe out of 48,803 probes assayed in the replication study cohort. Moreover, TYROBP was more differentially expressed in LOAD brains than the classical markers of microglia AIF1, and CD68, indicating there was not a relative down-regulation of TYROBP despite elevated microgliosis in LOAD brains (Perry et al., 2010).