Apolipoprotein E isoform mediated regulation of nitric oxide release 1,2 1Guest Editors: Mark A. Smith and George Perry 2This article is part of a series of reviews on “Causes and Consequences of Oxidative Stress in Alzheimer’s Disease.” The full list of papers may be found on the homepage of the journal.

Brown, Candice M.; Wright, Elizabeth J.; Colton, Carol A.; Sullivan, Patrick M.; Laskowitz, Daniel T.; Vitek, Michael P.

doi:10.1016/s0891-5849(02)00803-1

Cited by 74 publications

(18 citation statements)

References 27 publications

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“…Importantly, there is no difference among TR APOE cultures in expression of TLR4 or binding of LPS by apoE isoforms. We confirmed the results mentioned above [64, 65] that activated TR APOE4/4 microglia secrete more NO than TR APOE3/3 microglia and extended them to show that activated TR APOE2/2 are no different from wt [70]. However, in our study we also determined that detectable increase in medium NO occurs after paracrine neurotoxicity, thereby questioning the relevance of NO as neurotoxic effector in this model.…”

Section: Apoe Isoforms In the Regulation Of Innate Immunitysupporting

confidence: 91%

“…TR APOE mice derived by homologous recombination were developed by Sullivan and colleagues and contain chimeric genes consisting of mouse 5’ regulatory sequence continuous with mouse (noncoding) exon 1 followed by human exons (and introns) 2–4 to produce TR APOE2/2, TR APOE3/3, or TR APOE4/4 mice [62, 63]. Using these mice, Brown, Colton, and colleagues have shown that that activated TR APOE4/4 microglia secrete more NO than TR APOE3/3 microglia [64, 65] and have expanded their studies to include peritoneal macrophages and PIC, a selective activator of TLR3 [66]. TR APOE4/4 primary microglia display enhanced activation, including increased secretion of TNFα and IL-6, with subsequent induction of NOS2 expression and activity; similar effects were seen in peritoneal macrophages from TR APOE3/3 and TR APOE4/4 mice.…”

Section: Apoe Isoforms In the Regulation Of Innate Immunitymentioning

confidence: 99%

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Apolipoprotein E isoforms and regulation of the innate immune response in brain of patients with Alzheimer's disease

Keene

Cudaback

et al. 2011

Current Opinion in Neurobiology

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The largest genetic risk for late-onset Alzheimer’s disease (AD) resides at the apolipoprotein E gene (APOE) locus, which has three common alleles (ε2, ε3, ε4) that encode three isoforms (apoE2, apoE3, apoE4). The very strong association of the APOE ε4 allele with AD risk and its role in the accumulation of amyloid β and animal models solidify the biological relevance of apoE isoforms but do not provide mechanistic insight. The innate immune response is consistently observed in AD and is a likely contributor to neuronal injury and response to injury. Here we review emerging data showing that apoE isoform regulation of multiple facets of the innate immune response in the brain may alter AD not only through amyloid β-dependent mechanisms, but also through other, amyloid β-independent mechanisms.

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Section: Apoe Isoforms In the Regulation Of Innate Immunitysupporting

confidence: 91%

Section: Apoe Isoforms In the Regulation Of Innate Immunitymentioning

confidence: 99%

Apolipoprotein E isoforms and regulation of the innate immune response in brain of patients with Alzheimer's disease

Keene

Cudaback

et al. 2011

Current Opinion in Neurobiology

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“…Other non-traditional pathways have been proposed. For example, apo E4 allele carriers display increased presence of oxidative stress marker and increased plasma F2-isoprostane levels [28,29]. …”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E Polymorphism and the Progression of Diabetic Nephropathy in Type 2 Diabetes

Tien

Chou

et al. 2011

Am J Nephrol

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Background/Aims: Three different apo E alleles (E2, E3 and E4) produce apo E isoproteins, which regulate the metabolism of lipoproteins. This study investigated the apo E polymorphisms as a prognostic factor for the development of diabetic nephropathy (DN). Methods: A total of 525 type 2 diabetic patients were enrolled to participate in this prospective observational study. Apo E gene polymorphisms were analyzed by polymerase chain reaction. The progression of DN was defined as a shift to a higher stage of DN or a doubling of the baseline serum creatinine level by the end of the study. Results: The mean follow-up period was 42.4 months. The patients whose DN progressed had significantly higher urine albumin/creatinine ratios and fewer used diuretics than those in whom DN did not progress. In the Cox regression analysis, the apo E4 carriers were found to be at greater risk of progression of DN than non-apo E4 carriers (p = 0.007, hazard ratio 2.252). After adjusting for confounding factors, apo E4 carriers remained at increased risk of progression to more severe DN (p = 0.002, hazard ratio 2.820). Conclusion: Our study suggests the apo E4 carrier might serve as a predictor of DN progression in Taiwan.

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“…Adult macrophages from APOE4 -TR male mice produce significantly higher levels of nitric oxide (NO) than those from APOE3 -TR male mice, but female macrophages show no difference between APOE3 and APOE4 (Brown et al, 2002). The protective effect of sex-steroid hormones also varies with APOE status.…”

Section: Modifiers Of Alzheimer’s Disease Risk and Their Interaction mentioning

confidence: 99%

Interactions between inflammation, sex steroids, and Alzheimer’s disease risk factors

Uchoa

Moser

Pike

2016

Frontiers in Neuroendocrinology

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Alzheimer’s disease (AD) is an age-related neurodegenerative disorder for which there are no effective strategies to prevent or slow its progression. Because AD is multifactorial, recent research has focused on understanding interactions among the numerous risk factors and mechanisms underlying the disease. One mechanism through which several risk factors may be acting is inflammation. AD is characterized by chronic inflammation that is observed before clinical onset of dementia. Several genetic and environmental risk factors for AD increase inflammation, including apolipoprotein E4, obesity, and air pollution. Additionally, sex steroid hormones appear to contribute to AD risk, with age-related losses of estrogens in women and androgens in men associated with increased risk. Importantly, sex steroid hormones have anti-inflammatory actions and can interact with several other AD risk factors. This review examines the individual and interactive roles of inflammation and sex steroid hormones in AD, as well as their relationships with the AD risk factors apolipoprotein E4, obesity, and air pollution.

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Cited by 74 publications

References 27 publications

Apolipoprotein E isoforms and regulation of the innate immune response in brain of patients with Alzheimer's disease

Apolipoprotein E isoforms and regulation of the innate immune response in brain of patients with Alzheimer's disease

Apolipoprotein E Polymorphism and the Progression of Diabetic Nephropathy in Type 2 Diabetes

Interactions between inflammation, sex steroids, and Alzheimer’s disease risk factors

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