APOE and Alzheimer disease: Consistent with previous reports that ApoE4 is involved in ER stress and calcium signaling in AD pathogenesis [33–35], intracellular accumulation of ApoE protein and expression of the ER stress markers glucose regulated proteins (GRP78) and p-eIF2α (Ser 51) were significantly upregulated in microglia treated with ApoE4 in the presence of PHF than in the cells treated with ApoE3 in the presence or absence of PHF.