Table 1 APOE receptors
From: APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease
| APOE receptors | Isoform-specific binding | APOE lipidation required for receptor binding? | APOE binding related functions |
|---|---|---|---|
| LDLR | Lipidated APOE: APOE2 < <APOE3 = APOE4 [65, 66] | Yes [67,68,69] | Mediates lipoprotein and Aβ clearance [4, 70] |
| LRP1 | Lipidated APOE: APOE2 < APOE3 = APOE4 [71]; Non-lipidated APOE: APOE3 binds immobilized LRP1 recombinant cluster IV with a higher affinity than APOE4 [72] | Likely not required although one study suggests otherwise [67, 72, 73] | Mediates lipoprotein and Aβ clearance [70, 74]; signal transduction [15,16,17]; neurotrophic effect [16, 75,76,77,78,79,80]. |
| VLDLR | Non-lipidated APOE: APOE2 = APOE3 = APOE4 [67] | No [67] | Mediates lipoprotein and Aβ clearance [70, 81], as well as reelin signaling [82,83,84]. |
| APOER2/LRP8 | Non-lipidated APOE: APOE2 < <APOE3 = APOE4 [85] | No [85] | Mediates reelin signaling [82,83,84]; regulates intracellular trafficking of synaptic receptors [18]. |
| HSPG | Non-lipidated APOE: APOE2 < APOE3 < APOE4 [86] | No [41, 86] | Mediates lipoprotein and Aβ clearance [4, 70] |
| TREM2 | Both lipidated and non-lipidated APOE: APOE2 = APOE3 = APOE4 [62,63,64] | No [62,63,64] | Mediates microglial phagocytosis of Aβ and damaged neurons [64, 87, 88]; Maintains neurodegenerative phenotype (MGnD) of disease-associated microglia (DAM) [89, 90]. |