Skip to main content

Table 2 Summary of the association of APOE4 with greater neuroinflammation

From: Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4

Author Key findings
Cultures (microglia, astrocytes, or mixed cultures) and inflammatory response by genotype
Vitek et al. [28] Microglia derived from ApoE4-TR mice demonstrated increased NO production, increased Nos2 mRNA levels, and greater TNFα, IL6, IL12 levels compared to microglia from ApoE3-TR mice.
Colton et al. [29] Significantly more NO was produced in primary microglia and macrophages from ApoE4-TR mice compared to ApoE3-TR mice.
Guo et al. [30] The addition of exogenous ApoE4 induced greater IL1β than ApoE3 in rat mixed glial cells.
Chen et al. [31] ApoE4, but not ApoE3, stimulated secretion of PGE2 and IL-1β in rat primary microglia.
Shi et al. [32] Higher TNFα, IL1β, and IL1α levels were observed in primary microglia from ApoE4-TR mice stimulated with LPS than ApoE2 and ApoE3.
Tai et al. [33] Greater astrogliosis and microgliosis, higher levels of IL1β in APOE4-FAD mice compared with APOE_-FAD mice.
Zhu et al. [34] Higher levels of microglia/macrophage, astrocytes, and invading T-cells after LPS injection in ApoE4-TR mice than ApoE3-TR mice. ApoE4-TR mice also displayed greater and more prolonged increases of cytokines (IL1β, IL6, TNFα) than ApoE2-TR and ApoE3-TR mice.
Ophir et al. [35] The expression of inflammation-related genes (NF-κB response elements) following intracerebroventricular injection of LPS was significantly higher and more prolonged in ApoE4-TR than in ApoE3-TR mice.
Both human and mouse models
Gale et al. [36] ApoE4-TR mice displayed enhanced plasma cytokines after systemic LPS injection compared with ApoE3 counterparts. After intravenous LPS administration, APOE3/E4 patients had higher plasma TNF-α levels than APOE3/E3 patients.
Human brain studies of inflammation and oxidative stress studies by APOE genotype
Montine at al [37] Pyramidal neuron cytoplasm was immunoreactive for 4-hydroxy-2-nonenal (HNE) in 4 of 4 APOE4 homozygotes, 2 of 3 APOE3/E4 heterozygotes, and none of 3 APOE3 homozygotes
Ramassamy et al. [20] In hippocampal homogenates from AD brains, APOE4 carriers had greater levels of thiobarbituric acid-reactive substances (TBARS), lower catalase activities, and increased or decreased glutathione peroxidase and glutathione than tissues from patients homozygous for the APOE3 allele (n = 10 per group).
Egensperger et al. [38] The number of activated microglia and the tissue area occupied by these cells increased significantly with the APOE4 gene dose (n = 20).
Minett et al. [39] APOE4 allele was significantly related to greater expression of CD68, HLA-DR, and CD64 in microglia (n = 299).
Friedberg et al. [40] Cellular density of microglial marker-Iba1 was positively associated with tau pathology in APOE4 carrier participants only (n = 154).
Systemic inflammation and dementia risk by genotype
Tao et al. [19] Participants with APOE4 and elevated plasma C reactive protein (CRP) levels had a shortened latency for the onset of AD (n = 2562).