Table 1.
AD risk genes involved in inflammatory responses.
| Genes | TLR4 | References | Inflammasome | References | Complement | References | Functions |
|---|---|---|---|---|---|---|---|
| ABCA7 | No | No | No | Involved in lipid homeostasis; enhances Aβ clearance by macrophages (40, 41) | |||
| APOE | Yes | (42–44) | Maybe | (45) | Maybe | (46) | Involved in lipid metabolism (42–44) |
| CD33 | Yes | (47) | Maybe | (48) | Maybe | (49) | Inhibitory receptor exclusive to immune cells (47) |
| CLU | No | No | Yes | (50) | Inhibitor of complement receptors (50) | ||
| CR1 | Yes | (51) | Yes | (52) | Yes | (53) | Influences complement cascade; binds C1q; inhibits formation of MAC (52, 54) |
| EPHA1 | No | No | No | Promotes permeability of the blood-brain barrier (55, 56) | |||
| HLA-DRB1 | No | No | No | Creates beta chain 1 of the MHC class II protein complex | |||
| HLA-DRB5 | No | No | No | Creates beta chain 5 of the MHC class II protein complex | |||
| INPP5D | Yes | (57, 58) | No | No | Binds DAP12 which inactivates the TREM2-DAP12 signaling complex (59) | ||
| MEF2C | Maybe | (60) | No | No | Regulates apoptosis of T cells and is necessary for transcriptional activation of IL-2 (61, 62) | ||
| MS4A cluster (MS4A4E and MS4A6A) | Maybe | (63) | No | Maybe | (63) | Ligand binding promotes calcium conductance; may modulate TREM2 expression (and TLR/complement through TREM2) (63) | |
| TLR4 variant (rs4986790) | Yes | Yes | No | Altered ability to recruit MyD88 and TRIF (64) | |||
| TREM2 | Yes | (65, 66) | Maybe | (67) | Yes | (68, 69) | Found on myeloid cells and alters inflammatory functions (70) |