Does Nitric Oxide Synthase Contribute to the Pathogenesis of Alzheimer's Disease? Effects of β-Amyloid Deposition on NOS in Transgenic Mouse Brain with AD Pathology

Debomoy Lahiri, D. Chen, Y. W. Ge, Martin Farlow, G. Kotwal, A. Kanthasamy, D. K. Ingram, N. H. Greig

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Oxidative stress is a risk factor for Alzheimer's disease (AD) whose major hallmark includes brain depositions of the amyloid beta peptide (Aβ) derived from the β-amyloid precursor protein (APP). Our aim was to determine whether or not excessive Aβ deposition would alter nitric oxide synthase (NOS) activity, and thereby affect NOS-mediated superoxide formation. We compared NOS activity in brain extracts between Tg mice (expressing APP Swedish double mutation plus presenilin [PS-1] and nontransgenic [nTg] mice. Five brain regions, including cerebral cortex, hippocampus, cerebellum, and striatum from both nTg and Tg mice showed a detectable level of neuronal (n) NOS activity. Cerebellar extracts from both nTg and Tg mice displayed the highest level of nNOS activity, which was fourfold higher than cortical extracts. Although there was an increase in nNOS activity in Tg brain extracts, this did not attain statistical significance. A similar result was obtained for inducible NOS levels. Our results suggest that excess levels of Aβ failed to both trigger NOS activity and change NOS levels.

Original languageEnglish
Pages (from-to)639-642
Number of pages4
JournalAnnals of the New York Academy of Sciences
Volume1010
DOIs
StatePublished - 2003

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Pathology
Amyloid
Nitric Oxide Synthase
Transgenic Mice
Brain
Alzheimer Disease
Amyloid beta-Protein Precursor
Presenilin-1
Nitric Oxide Synthase Type I
Presenilins
Amyloid beta-Peptides
Nitric Oxide Synthase Type II
Oxidative stress
Superoxides
Cerebral Cortex
Cerebellum
Hippocampus
Oxidative Stress
Alzheimer's Disease
Deposition

Keywords

  • Aging
  • Beta-protein
  • Dementia
  • Free radicals
  • Neurodegeneration
  • Nitric oxide
  • Oxidative stress
  • ROS

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Does Nitric Oxide Synthase Contribute to the Pathogenesis of Alzheimer's Disease? Effects of β-Amyloid Deposition on NOS in Transgenic Mouse Brain with AD Pathology. / Lahiri, Debomoy; Chen, D.; Ge, Y. W.; Farlow, Martin; Kotwal, G.; Kanthasamy, A.; Ingram, D. K.; Greig, N. H.

In: Annals of the New York Academy of Sciences, Vol. 1010, 2003, p. 639-642.

Research output: Contribution to journalArticle

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