Nox2-derived Radicals Contribute to Neurovascular and Behavioral Dysfunction in Mice Overexpressing the Amyloid Precursor Protein

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Jan 19

PMID 18202172

Citations 199

Authors

Laibaik Park

Ping Zhou

Rose Pitstick

Carmen Capone

Josef Anrather

Erin H Norris

Linda Younkin

Steven Younkin

George Carlson

Bruce S McEwen

Costantino Iadecola

Affiliations

Soon will be listed here.

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.

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