FIGURE 7.

ApoE4 mediated impaired calcium homeostasis. Path A: Elevated calcium influx through L‐VGCCs and NMDARs results in an elevated level of intracellular calcium. A Dab1/SFK mediated pathway downstream of ApoE binding to APOERs promotes NMDAR mediated calcium influx. ApoE4 binding to LDLR/LRP family receptors upregulates MAPK signalling activation and is linked to activation of cFos/CREB synaptogenic signalling which may be chronically dysregulated. Path B: In astrocytes ApoE4 has been shown to induce the release of calcium from intracellular stores such as the mitochondria and endo/lysosomal compartments. The net effect of these pathways is a prolonged increase in intracellular calcium concentration, calcium signalling and subsequent cell death. Abbreviations: APOER, apolipoprotein E receptor; ApoE4, apolipoprotein E4; cFos, FBJ osteosarcoma oncogene; CREB, cyclic adenosine monophosphate (cAMP) response element binding protein; Dab1, disabled 1; L‐VGCCs, L type voltage gated calcium channels; LRP1, Lowdensity lipoprotein receptor‐related protein 1; MAPK, mitogen activated protein kinase; NMDAR, N‐methyl‐daspartate receptor; SFK, serine family kinases. Created with BioRender.com