Table 1.

Selected studies on APOE and endoplasmic reticulum stress

Reference	Model system	ER stress-relevant findings in E4-carrying cells
Sabaretnam et al. [80]	APOE4 vs. APOE3 transfected HepG2 cells	- Trafficking velocity ↓
Zhong et al. [75]	Primary astrocytes from Arg-61 APOE mice vs. wild type mice astrocytes	- Intracellular APOE concentration↓ - Levels and fragmentation of Oasis ↑ - Levels of UPR components and downstream effectors (ATF4, XBP1, BIP, GRP94, PDI, GADD34, Herp, CHOP) ↑
Brodbeck et al. [76]	EGFP-APOE4 vs. EGFP-APOE3 transfected Neuro-2a cells and primary murine hippocampal neurons	- Retention of APOE in Golgi and ER ↑ - Trafficking of APOE in the Golgi/Soma ↓ - PERK, ATF6, XBP1, IRE1ɑ, CHOP, BIP protein levels ↔ Impaired EGFP-APOE4 trafficking rescued by R61T mutation or APOE4 structure correctors.
Eberlé et al. [78]	Primary peritoneal macrophages from Arg-61 APOE vs. Thr-61 APOE mice	- APOE secretion ↓ - ATF4, CHOP, TRB3 mRNA levels ↔
Cash et al. [79]	Primary peritoneal macrophages from APOE4 vs. APOE3 TR mice	- Inflammation-induced apoptosis ↑ - Efferocytosis ↓ - Basal and stimulated conditions: JNK phosphorylation ↑ - Stimulated conditions: IRE1ɑ, PERK phosphorylation ↑ XBP1(S), CHOP mRNA and protein levels ↑ Improved efferocytosis, reduced apoptosis after tauroursodeoxycholic acid treatment.
Simpson et al. [81]	Human astrocyte transcriptome (lateral temporal cortex; APOE ε4 carriers vs. non-carriers)	Altered pathways incl. transcription (ATF4, FOXN3) and ubiquitin-mediated proteolysis (ATG7, UBA5)
Segev et al. [77]	APOE4 vs. APOE3 TR mice (age: 4 months, cortex and hippocampus)	- Phosphorylation of eIF2ɑ, GCN2, PKR ↑

ATF4 activating transcription factor 4, ATF6 activating transcription factor 6, ATG7 autophagy related 7, APOE apolipoprotein E, BIP binding immunoglobulin protein, CHOP c/EBP-homologous protein 10, EGFP enhanced green fluorescent protein, ER endoplasmic reticulum, FOXN3 forkhead box N3, GADD34 protein phosphatase 1, regulatory subunit 15A, GCN eukaryotic translation initiation factor 2 alpha kinase 4, GRP94 heat shock protein 90, beta, HERP homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1, IRE1α serine/threonine-protein kinase/endoribonuclease, JNK mitogen-activated protein kinase 8, OASIS old astrocyte specifically induced substance, PDI protein disulfide isomerase associated 3, PERK eukaryotic translation initiation factor 2-alpha kinase 3, PKR eukaryotic translation initiation factor 2-alpha kinase 2, TRB3 tribbles homolog 3, UBA5 ubiquitin like modifier activating enzyme 5, XBP1 X-box binding protein 1