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

Laibaik Park, Ping Zhou, Rose Pitstick, Carmen Capone, Josef Anrather, Erin H. Norris, Linda Younkin, Steven G Younkin, George Carlson, Bruce S. McEwen, Costantino Iadecola

Research output: Contribution to journalArticle

215 Citations (Scopus)

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-β peptide (Aβ) 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.

Original languageEnglish (US)
Pages (from-to)1347-1352
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number4
DOIs
StatePublished - Jan 29 2008

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Amyloid beta-Protein Precursor
Amyloid
Alzheimer Disease
NADPH Oxidase
Oxidative Stress
Amyloid Plaques
Blood Vessels
Reactive Oxygen Species
Catalytic Domain
Pathology
Mutation
Brain
Cognitive Dysfunction

Keywords

  • Alzheimer's disease
  • Cerebral blood flow
  • tg2576

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Nox2-derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein. / Park, Laibaik; Zhou, Ping; Pitstick, Rose; Capone, Carmen; Anrather, Josef; Norris, Erin H.; Younkin, Linda; Younkin, Steven G; Carlson, George; McEwen, Bruce S.; Iadecola, Costantino.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 4, 29.01.2008, p. 1347-1352.

Research output: Contribution to journalArticle

Park, Laibaik ; Zhou, Ping ; Pitstick, Rose ; Capone, Carmen ; Anrather, Josef ; Norris, Erin H. ; Younkin, Linda ; Younkin, Steven G ; Carlson, George ; McEwen, Bruce S. ; Iadecola, Costantino. / Nox2-derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 4. pp. 1347-1352.
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