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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Colton, CA; Needham, LK; Brown, C; Cook, D; Rasheed, K; Burke, JR; Strittmatter, WJ; Schmechel, DE; Vitek, MP

Published Date

  • February 2004

Published In

Volume / Issue

  • 147 / 1-2

Start / End Page

  • 62 - 67

PubMed ID

  • 14741429

International Standard Serial Number (ISSN)

  • 0165-5728

Digital Object Identifier (DOI)

  • 10.1016/j.jneuroim.2003.10.015


  • eng

Conference Location

  • Netherlands