TABLE 2.
Alzheimer’s disease risk-loci with proposed immune functions.
| SNP ID | Proposed gene | Immune function |
| Cytokine signaling | ||
| rs2305421 | ADAM10 | Cleaves TNFα (Mezyk-Kopec et al., 2009) |
| rs679515, rs3818361 | CR1 | Complement receptor, Aβ clearance (Rogers et al., 2006) |
| rs2965101, rs2927438 | BCL3 | Regulator of NF-kB (immune cell survival and inflammatory response) (Poveda et al., 2017) |
| rs11136000 | CLU | Inhibition of complement system, lipid transport, cell survival (Foster et al., 2019) |
| rs8100183 | MARK4 | Limits inflammasome (Li et al., 2017) |
| rs4420638 | APOC1 | Inhibits pro-inflammatory cytokine secretion from astrocytes and microglia (Cudaback et al., 2012) |
| Phagocytosis and microglial function | ||
| rs3865444, rs3826656 | CD33 | Phagocytosis (Griciuc et al., 2013) |
| rs558678, rs554311 rs610932, rs11824773 rs10897011, rs7926729 rs610932, rs983392 | MS4A2 MS4A4A MS4A4E MS4A6A | Immune and complement systems regulation and phagocytosis, TREM2 regulation (Ma et al., 2015; Deming et al., 2019) |
| rs75932628 | TREM2 | Phagocytosis, microglia migration and activation (Gratuze et al., 2018) |
| rs9381040 | TREML2 | Immune activation, phagocytosis (Zheng H. et al., 2016) |
| rs3851179, rs541458 | PICALM | Endocytosis and Aβ clearance (Zhao et al., 2015) |
| rs3764650, rs3752246 | ABCA7 | Mediates phagocytic, involved in microglial Aβ clearance (Aikawa et al., 2018) |
| rs616338 | ABI3 | Microglial function, actin polymerization (Satoh et al., 2017) |
| rs35349669 | INPP5D | Microglia function and survival (Efthymiou and Goate, 2017) |
| Lysosomes | ||
| rs597668 | BLOC1S3 | Lysosome biogenesis (Zhang et al., 2014) |
| rs8093731 | DSG2 | Lysosomal function (Karch and Goate, 2015) |
| rs5848 | GRN | Lysosomal function (Paushter et al., 2018) |
| Astrocytes and lipid metabolism | ||
| rs5167 | APOC4 | Lipid metabolism (Riedel et al., 2016) |
| rs2075650 | APOE | Lipid metabolism, immunomodulation, interacts with TREM2 (Shi and Holtzman, 2018) |
| Immune cell movement and migration | ||
| rs11767557, rs11771145 | EPHA1 | Immune cell trafficking (Yamazaki et al., 2009) |
| rs28834970 | PTK2B | Inflammation, microglia polarization (Okigaki et al., 2003) |
| Adaptive immune system | ||
| rs9271192 | HLA-DRB5-DBR1 | Antigen presentation (Karch and Goate, 2015) |
| rs2301275 | PVR | NK and T cell function (Stamm et al., 2018a, b) |
| rs2376866 rs117612135 | RELB | Dendritic cell differentiation, regulation of adaptive immune response (Zanetti et al., 2003) |
| rs190982 | MEF2C | B cell proliferation and antigen presentation (Sao et al., 2018) |