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Cultures (microglia, astrocytes, or mixed cultures) and inflammatory response by genotype
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Vitek et al. [28]
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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.
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Colton et al. [29]
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Significantly more NO was produced in primary microglia and macrophages from ApoE4-TR mice compared to ApoE3-TR mice.
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Guo et al. [30]
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The addition of exogenous ApoE4 induced greater IL1β than ApoE3 in rat mixed glial cells.
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Chen et al. [31]
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ApoE4, but not ApoE3, stimulated secretion of PGE2 and IL-1β in rat primary microglia.
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Shi et al. [32]
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Higher TNFα, IL1β, and IL1α levels were observed in primary microglia from ApoE4-TR mice stimulated with LPS than ApoE2 and ApoE3.
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Tai et al. [33]
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Greater astrogliosis and microgliosis, higher levels of IL1β in APOE4-FAD mice compared with APOE_-FAD mice.
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Zhu et al. [34]
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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.
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Ophir et al. [35]
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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.
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Both human and mouse models
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Gale et al. [36]
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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.
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Human brain studies of inflammation and oxidative stress studies by APOE genotype
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Montine at al [37]
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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
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Ramassamy et al. [20]
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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).
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Egensperger et al. [38]
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The number of activated microglia and the tissue area occupied by these cells increased significantly with the APOE4 gene dose (n = 20).
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Minett et al. [39]
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APOE4 allele was significantly related to greater expression of CD68, HLA-DR, and CD64 in microglia (n = 299).
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Friedberg et al. [40]
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Cellular density of microglial marker-Iba1 was positively associated with tau pathology in APOE4 carrier participants only (n = 154).
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Systemic inflammation and dementia risk by genotype
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Tao et al. [19]
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Participants with APOE4 and elevated plasma C reactive protein (CRP) levels had a shortened latency for the onset of AD (n = 2562).
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