In Alzheimer's disease (AD), affected neurons accumulate beta amyloid protein, components of which can induce mouse microglia to express the high-output isoform of nitric oxide synthase (NOS2) in vitro. Products of NOS2 can be neurotoxic. In mice, NOS2 is normally suppressed by transforming growth factor beta 1 (TGF-beta 1). Expression of TGF-beta 1 is decreased in brains from AD patients, a situation that might be permissive for accumulation of NOS2. Accordingly, we investigated the expression of NOS2 in patients with AD, using three monospecific antibodies: a previously described polyclonal and two new monoclonal antibodies. Neurofibrillary tangle-bearing neurons and neuropil threads contained NOS2 in brains from each of 11 AD patients ranging in age from 47 to 81 years. NOS2 was undetectable in brains from 6 control subjects aged 23-72 years, but was expressed in small amounts in 3 control subjects aged 77-87 years. Thus, human neurons can express NOS2 in vivo. The high-output pathway of NO production may contribute to pathogenesis in AD.
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1 October 1996
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October 01 1996
Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease.
Y Vodovotz,
Y Vodovotz
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
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M S Lucia,
M S Lucia
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
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K C Flanders,
K C Flanders
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
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L Chesler,
L Chesler
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
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Q W Xie,
Q W Xie
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
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T W Smith,
T W Smith
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
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J Weidner,
J Weidner
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
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R Mumford,
R Mumford
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
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R Webber,
R Webber
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
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C Nathan,
C Nathan
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
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A B Roberts,
A B Roberts
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
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C F Lippa,
C F Lippa
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
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M B Sporn
M B Sporn
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
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Y Vodovotz
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
M S Lucia
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
K C Flanders
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
L Chesler
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
Q W Xie
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
T W Smith
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Weidner
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
R Mumford
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
R Webber
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
C Nathan
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
A B Roberts
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
C F Lippa
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
M B Sporn
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 184 (4): 1425–1433.
Citation
Y Vodovotz, M S Lucia, K C Flanders, L Chesler, Q W Xie, T W Smith, J Weidner, R Mumford, R Webber, C Nathan, A B Roberts, C F Lippa, M B Sporn; Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease.. J Exp Med 1 October 1996; 184 (4): 1425–1433. doi: https://doi.org/10.1084/jem.184.4.1425
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