Table 1.
Gene expression in CVN-AD CD11c+ microglia compared with CVN-AD CD11c− microglia, C57BL/6 microglia, and mNos2−/− microgliaa
| Gene | Name | Fold change | p value | Reported actions | References |
|---|---|---|---|---|---|
| Mamdc | MAM domain containing protein 2 | 515 | 9.7 × 10−7 | Glycosaminoglycan binding, linked to negative regulation of synapses | Pettem et al., 2013 |
| Spp1 | Secreted phosphoprotein 1; osteopontin | 515 | 5.9 × 10−6 | Increased in CSF of AD patients; enhances immunosuppression | Comi et al., 2010; Sangaletti et al., 2014 |
| Gpnmb | Glycoprotein-transmembrane nmb; osteoactivin, Fe65-like1 | 442 | 1.5 × 10−6 | Tissue repair, M2 state; phagocytic vesicle processing | Duffield, 2010 |
| Wfdc17 | Whey acidic protein four disulfide core domain 17; AMWAP | 136 | 4.1 × 10−5 | Overexpression increases Arg-1, reduces IL-6, IL-1β | Karlstetter et al., 2010 |
| Itgax | Integrin alpha X (complement component 3 receptor 4 subunit), CD11c | 124 | 5.8 × 10−6 | Leukocyte-specific integrin; associated with dendritic cells; phagocytosis of complement-coated particles; found on microglia in AD | Akiyama and McGeer, 1990; Tooyama et al., 1990; Becher and Antel, 1996; Butovsky et al., 2007 |
| Gp49a | Glycoprotein 49a; Lirb4 | 107 | 2.8 × 10−4 | Member of inhibitory Ig superfamily; increased IL-4; suppresses LPS; inhibits Fc-gamma-mediated phagocytosis | Arm et al., 1997; McCormick et al., 1999 |
| Gng12 | Guanine nucleotide binding protein 12 | 64 | 1.7 × 10−4 | Inhibits LPS-mediated pro-inflammation | Larson et al., 2010 |
| Pdcd1 | Programmed cell death 1; PD-L1, CD279 | 51 | 4.1 × 10−6 | Immunoglobin superfamily; shifts microglia to M2 phenotype; regulates Arg-1 activity | Yao et al., 2014 |
| Apbb2 | Amyloid precursor protein binding protein 2 | 25.8 | 2.4 × 10−4 | Adaptor protein binds to cytoplasmic domain of APP; polymorphisms associated with dementia in aged population; involved in ECM synthesis by Macs | Wright et al., 2005; Grupe et al., 2006; Golanska et al., 2013 |
| TIMP2 | Tissue inhibitor of metalloprotease-2 | 20.7 | 3.2 × 10−4 | Blocks metalloprotease activity; associated with M2 phenotype | Ridnour et al., 2007; Wilcock et al., 2011a |
| Igf1 | Insulin-like growth factor 1; 2; somatomedin c | 27.4 | 2.0 × 10−5 | Found in human microglia, protects from IL-1- and IFN-γ-mediated damage; promotes Aβ clearance | Trueba-Sáiz et al., 2013 |
| Igf2 | 8.0 | 2.1 × 10−3 | |||
| Apoe | Apolipoprotein E | 20.1 | 3.6 × 10−4 | Strongest single gene risk factor for AD, suppresses proinflammatory cytokines | Saunders et al., 1996 |
| CD200r | Cell surface glycoprotein CD200 receptor 2, OX2R | 13.8 | 3.3 × 10−3 | Inhibitory immune receptor found on microglia, marker for M2 activation in human MG, less so in mice | Denieffe et al., 2013; Walker and Lue, 2013 |
| Klf6 | Kruppel-like factor 6 | 0.12 | 4.9 × 10−6 | Suppression is linked to M2 phenotype | Date et al., 2014 |
| Apobec3 | Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 | 0.18 | 4.1 × 10−4 | Promotes antiviral immunity through production of neutralizing antibody | Santiago et al., 2008 |
| Ifngr1 | Interferon-γ receptor 1; CD119 | 0.19 | 9.1 × 10−6 | Encodes ligand binding domain for IFN-γ; downregulated by TLR2; IFN-β | Curry et al., 2004; Kearney et al., 2013 |
| Siglech | Siglec-H | 0.42 | 2.6 × 10−4 | DAP12 signaling molecule, microglial “sensome,” decreased with aging | Hickman et al., 2013 |
aSelect genes that were significantly upregulated or downregulated in CVN-AD CD11c+ microglia compared with CVN-AD CD11c− microglia, C57BL/6 microglia, and mNos2−/− microglia, including fold change in expression, p value, and reported actions with references.