APOE genotype-specific differences in human and mouse macrophage nitric oxide production

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 producti...

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Bibliographic Details
Published in:Journal of neuroimmunology 2004-02, Vol.147 (1), p.62-67
Main Authors: Colton, Carol A., Needham, Leila K., Brown, Candice, Cook, Danielle, Rasheed, Karima, Burke, James R., Strittmatter, Warren J., Schmechel, Donald E., Vitek, Michael P.
Format: Article
Language:English
Subjects:
Aged
Alzheimer Disease - blood
Alzheimer Disease - complications
Alzheimer Disease - genetics
Alzheimer's disease
Animals
Apolipoprotein E3
Apolipoprotein E4
Apolipoproteins E - deficiency
Apolipoproteins E - genetics
Case-Control Studies
Cells, Cultured
dementia
Dementia - blood
Dementia - complications
Dementia - genetics
Female
Genotype
Humans
Low Density Lipoprotein Receptor-Related Protein-1 - metabolism
Macrophages
Macrophages - metabolism
Male
Mice
Mice, Knockout
Microglia
Microglia - enzymology
Middle Aged
Monocytes - enzymology
Neuroinflammation
Nitric oxide
Nitric Oxide - metabolism
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
Reactive oxygen species
Reverse Transcriptase Polymerase Chain Reaction - methods
RNA, Messenger - biosynthesis
Species Specificity
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Description
Summary: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.
ISSN:0165-5728
1872-8421
DOI:10.1016/j.jneuroim.2003.10.015