TABLE 1.
Genes in microglia associated with AD.
| Gene | Variant | Protein description | Related functions |
| APOE (Serrano-Pozo et al., 2021) | 3 common variants or isoforms: APOE2 decreases, although APOE4 increases LOAD risk relative to APOE3 | Major apolipoprotein in brain HDL-like particles | Chaperone Aβ and lipids; endocytosis; phagocytosis |
| NME8 (Lambert et al., 2013) | rs2718058 | Encodes protein with thioredoxin and nucleoside diphosphate kinase domains | Unknown function |
| CD33 (Griciuc et al., 2019) | rs12459419 | Binds sialylated ligands; phosphorylated ITIM recruits phosphatase SHP-1 | ITIM signaling; phagocytosis inhibition |
| MEF2C (Lynch et al., 2005) | rs190982 | Widely studied in muscle cells and neurons | Microglia activation |
| TREM2 (Liu et al., 2020; Hardy and Salih, 2021) | rare coding LOF variants: R47H, R62H, T66M, H157Y | Binds anionic/lipophilic ligands; triggers DAP12 ITAM to recruit kinase Syk | ITAM signaling; Phagocytosis; inflammation |
| INPP5D (Tsai et al., 2021; Lin et al., 2022) | rs35349669 | SH3-containing inositol phosphatase, converts phosphatidylinositol (3,4,5)-trisphosphate to phosphatidylinositol (3,4)-bisphosphate | Endocytosis; phagocytosis |
| PLCG2 (Sims et al., 2017; Tsai et al., 2022) | rare P522R coding GOF variant | Phospholipase activity cleaves phosphatidylinositol (4,5)-bisphosphate into IP3 and DAG second messengers | TREM2 signaling; phagocytosis; inflammation |
| CD2AP (Tao et al., 2019) | rs10948363, rs9296559 and rs9349407 | Scafolding protein co-localizing with F-actin | Phagocytosis; phagosome formation |
| LILRB4 (Salih et al., 2019) | rs731170 | ITIM-containing transmembrane receptor | ITIM signaling |
| CR1 (Zhu et al., 2015) | rs6656401 | Complement receptor 1; binds C1q and C3b/C4b | Complement system cascade; phagocytosis |
| EPHA1 (Talebi et al., 2020; Buhl et al., 2022) | rs11771145, rs11767557 | Receptor tyrosine kinase for ephrin-A class ligands | Eph/ephrin signaling |
| SCIMP (Schwartzentruber et al., 2021) | rs61182333 | Non-TIR-containing TLR adaptor protein | TLR signaling; phagocytosis |
| SHARPIN (Schwartzentruber et al., 2021) | rs78541244 | Subunit of LUBAC regulating NF-κB and MAPK signaling | NF-κB pathway; inflammation |
| ITGAM (Salih et al., 2019) | rs79113991 | Encode integrin CD11b | Phagocytosis |
| PTK2B (Combs et al., 1999; Li et al., 2016) | rs28834970 | Non–receptor tyrosine kinase; homolog of focal adhesion kinase | Actin cytoskeletal rearrangement; phagocytosis |
| CASS4 (Beck et al., 2014) | rs7274581 | Scaffold protein associated with focal adhesion kinases FAK, Pyk2 | Focal adhesion; cytoskeletal rearrangement |
| ABI3 (Sekino et al., 2015) | rare coding variant S209F | Component of the Abi/WAVE complex involved in actin polymerization | Motility; phagocytosis |
| RIN3 (Kajiho et al., 2011) | rs10498633 | a guanine nucleotide exchange factor for Rab5 and Rab31 | early endocytic pathway |
| PICALM (Ando et al., 2022) | rs3851179, rs541458 | Endocytic adaptor | Endo-lysosomal trafficking; phagocytosis |
| FERMT2 (Eysert et al., 2021) | rs17125944 | Adaptor between membrane and actin cytoskeleton at extracellular matrix adhesion sites | Actin polymerization; focal adhesion |
| BIN1 (Gao et al., 2021) | rs6733839, rs744373 | Involved in membrane curvature and dynamin interaction | Endocytosis; phagocytosis |
| HLA-DRB1 (Ghosh et al., 2013) | rs9271192 | Major histocompatibility complex class II protein for extracellular antigen presentation | Phagocytosis |
| RAB10 (Tavana et al., 2019) | rs95684712 | Rab superfamily member | Endosomal trafficking and fusion |
| SPI1 (Cao et al., 2022) | rs1057233 | Transcription factor PU.1 | Gene expression |
| SORL1 (Mishra et al., 2022) | 17 coding variants identified, some common and rare | Receptor for vesicular sorting of lipoproteins and various receptors | Endo-lysosomal network; lipid metabolism; |
| SPPL2A (Lambert et al., 2013; Schwartzentruber et al., 2021) | rs12592778 | Aspartyl protease in late endosomes and lysosomes | Inflammation |
| GRN (Schwartzentruber et al., 2021) | rs5848 | Lysosomal protein | Lysosomal degradation |
| ABCA7 (Zhao et al., 2015) | rs3764650, rare coding LOF variants | ATP-binding cassette transporter; multipass transmembrane protein transports lipids | Phagocytosis |
| MS4A (Deming et al., 2019) | rs983392 | Four-pass transmembrane protein in MS4A family | Microglial receptor complex |
| ZCWPW1 (Karch et al., 2016) | rs1476679 | Presumed epigenetic regulator through its chromatin-binding domains | Immune receptors |