CD33 (6.02 ± 0.41), TREM2 (4.86 ± 0.50, and APOE (2.52 ± 0.19), genes implicated in Aβ clearance/degradation. BDTOs increased expression of 4 genes including CD2AP (4.62 ± 0.45), previously implicated in tau-mediated toxicity (Shulman et al., 2014). In addition, 6 genes were differentially elevated in fAβ compared to BDTOs (Table S3). Interestingly, CD33, TYROBP, and PICALM, genes more enriched in other myeloid cells at baseline, were upregulated by fAβ and BDTOs suggesting that proteinopathies may alter microglia phenotype to resemble invading peripheral myeloid cells (Chan et al., 2007; Prinz et al., 2011; Stalder et al., 2005). In addition to AD GWAS genes, iMGLs express other CNS disease-related genes including APP, PSEN1/2, HTT, GRN, TARDBP, LRRK2, C9orf72, SOD1, VCP, and FUS and therefore, can likely be used to study other neurological diseases such as ALS, HD, FTD, and DLB in which microglia may play a prominent role (Bachstetter et al., 2015; Crotti et al., 2014; Lui et al., 2016; O’Rourke et al., 2016)(Figure S6C).
