APOE genotype-specific differences in human and mouse macrophage nitric oxide production
Abstract
Individuals expressing an APOE4 genotype demonstrate increased Alzheimer's disease (AD) neuropathology and a decreased onset age. The APOE4 gene may act by modulating the CNS immune response. Using human monocyte-derived macrophages (MDM), we show a significantly greater increase in NO production during immune activation in MDM from APOE4 AD patients compared to normal, age-matched individuals or to AD patients with an APOE 3/3 genotype. Microglia and peritoneal macrophages from APOE4 targeted replacement mice demonstrate a similar increase in NO compared to the APOE3 targeted replacement mice. The enhanced macrophage responsiveness and the increased production of NO in APOE4 AD patients may predispose the CNS to an increased potential for nitration and nitrosation, consistent with the redox imbalance and neuroinflammatory state seen in AD.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
After intravenous administration of LPS, apoE4 knock-in mice had greater inflammatory responses compared with apoE3 knock-in mice.
“After intravenous administration of LPS, apoE4 knock-in mice had greater inflammatory responses compared with apoE3 knock-in mice (Colton et al., 2004; Lynch et al., 2003).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Colton et al., 2004
Cites
Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease
Itagaki, S., McGeer, P. L., Akiyama, H., Zhu, S., & Selkoe, D. (1989) · Journal of Neuroimmunology · doi:10.1016/0165-5728(89)90115-x · Cited by 940 · see citing works
McGeer, P. L., Itagaki, S., Tago, H., & McGeer, E. G. (1987) · Neuroscience Letters · doi:10.1016/0304-3940(87)90696-3 · Cited by 836 · see citing works
Sullivan, P. M., Mezdour, H., Quarfordt, S. H., & Maeda, N. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2673 · Cited by 254 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · see citing works
Apolipoprotein E in Alzheimer’s disease and other neurological disorders
Verghese, P. B., Castellano, J. M., & Holtzman, D. M. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70325-2 · Cited by 857 · see citing works
Claxton, A., Baker, L. D., Hanson, A., Trittschuh, E. H., Cholerton, B., Morgan, A., Callaghan, M., Arbuckle, M., Behl, C., & Craft, S. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-141791 · Cited by 467 · see citing works
Smith, A. M., & Dragunow, M. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2013.12.001 · Cited by 256 · see citing works
Human APOE4 increases microglia reactivity at Aβ plaques in a mouse model of Aβ deposition
Rodriguez, G. A., Tai, L. M., LaDu, M. J., & Rebeck, G. W. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-111 · Cited by 193 · see citing works
- Authors
- Colton, C. A., Needham, L. K., Brown, C., Cook, D., Rasheed, K., Burke, J. R., Strittmatter, W. J., Schmechel, D. E., & Vitek, M. P.
- Affiliations
- Duke University (US)
- Corresponding author
- Colton, Carol A.
- Venue
- Journal of Neuroimmunology
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 147
- Issue
- 1-2
- Pages
- 62-67
- ISSN
- 0165-5728 (ISSN-L)
- OpenAlex
- W2053840148
- Cited by
- 75
- References
- 3
- Citations by year
- 2022: 3 · 2021: 3 · 2020: 3 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 2 · 2012: 5
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroimmunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG05 128, P50AG005128)
- National Institute of Neurological Disorders and Stroke (NS 36728, R01NS036728, NS 41443)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- APOE ε4, APOE genotype, nitric oxide production, macrophages, monocyte-derived macrophages, Alzheimer's disease, microglia, peritoneal macrophages, targeted replacement mice, neuroinflammation, redox imbalance, CNS immune response
- MeSH terms
- Aged, Alzheimer Disease, Animals, Apolipoproteins E, Cells, Cultured, Dementia, Female, Genotype, Humans, Macrophages, Male, Middle Aged, Monocytes, Nitric Oxide, RNA, Messenger, Species Specificity, Case-Control Studies, Microglia, Mice, Knockout, Nitric Oxide Synthase, Reverse Transcriptase Polymerase Chain Reaction, Low Density Lipoprotein Receptor-Related Protein-1, Mice, Nitric Oxide Synthase Type II, Apolipoprotein E3, Apolipoprotein E4
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
