Nox2-derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein Academic Article uri icon

Overview

MeSH Major

  • Amyloid beta-Protein Precursor
  • Behavioral Symptoms
  • Brain
  • Free Radicals
  • Hyperemia
  • Membrane Glycoproteins
  • NADPH Oxidase

abstract

  • Alterations in cerebrovascular regulation related to vascular oxidative stress have been implicated in the mechanisms of Alzheimer's disease (AD), but their role in the amyloid deposition and cognitive impairment associated with AD remains unclear. We used mice overexpressing the Swedish mutation of the amyloid precursor protein (Tg2576) as a model of AD to examine the role of reactive oxygen species produced by NADPH oxidase in the cerebrovascular alterations, amyloid deposition, and behavioral deficits observed in these mice. We found that 12- to 15-month-old Tg2576 mice lacking the catalytic subunit Nox2 of NADPH oxidase do not develop oxidative stress, cerebrovascular dysfunction, or behavioral deficits. These improvements occurred without reductions in brain amyloid-beta peptide (Abeta) levels or amyloid plaques. The findings unveil a previously unrecognized role of Nox2-derived radicals in the behavioral deficits of Tg2576 mice and provide a link between the neurovascular dysfunction and cognitive decline associated with amyloid pathology.

publication date

  • January 29, 2008

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2234141

Digital Object Identifier (DOI)

  • 10.1073/pnas.0711568105

PubMed ID

  • 18202172

Additional Document Info

start page

  • 1347

end page

  • 52

volume

  • 105

number

  • 4