Modulation of nitric oxide production in human macrophages by apolipoprotein-E and amyloid-beta peptide.

Journal Article (Journal Article)

Induction of oxidative stress has been implicated as a causative factor in chronic neurodegenerative diseases such as Alzheimer's disease. Apolipoprotein-E (apoE) and amyloid-beta peptide (A beta) have been reported to alter the redox state of the brain. Using human monocyte-derived macrophages as a model of brain microglia, physiological levels of apolipoprotein-E were found to stimulate nitric oxide (NO) production in polyinosinic:polycytidylic acid (poly I:C) primed cells. ApoE treatment released 68% more NO than cells treated with poly I:C alone and almost threefold more NO than unprimed cells. In contrast to mouse microglia, human cells failed to generate NO in response to A beta peptides, with or without poly I:C treatments. Furthermore, the combination of A beta plus apoE inhibited the increase in NO production induced by apoE. Since Alzheimer's is strongly associated with the presence of an APOE4 allele, our study predicts a mechanism where apoE and A beta regulate nitric oxide production in human brain.

Full Text

Duke Authors

Cited Authors

  • Vitek, MP; Snell, J; Dawson, H; Colton, CA

Published Date

  • November 17, 1997

Published In

Volume / Issue

  • 240 / 2

Start / End Page

  • 391 - 394

PubMed ID

  • 9388488

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1006/bbrc.1997.7408


  • eng

Conference Location

  • United States