title: Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease.
abstract: 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.
authors.affiliation: Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Vodovotz
authors.forename: M S
authors.initials: MS
authors.lastname: Lucia
authors.forename: K C
authors.initials: KC
authors.lastname: Flanders
authors.forename: L
authors.initials: L
authors.lastname: Chesler
authors.forename: Q W
authors.initials: QW
authors.lastname: Xie
authors.forename: T W
authors.initials: TW
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Weidner
authors.forename: R
authors.initials: R
authors.lastname: Mumford
authors.forename: R
authors.initials: R
authors.lastname: Webber
authors.forename: C
authors.initials: C
authors.lastname: Nathan
authors.forename: A B
authors.initials: AB
authors.lastname: Roberts
authors.forename: C F
authors.initials: CF
authors.lastname: Lippa
authors.forename: M B
authors.initials: MB
authors.lastname: Sporn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000302:isolation & purification*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000302:isolation & purification*
chemical_list: D000911:Antibodies, Monoclonal; D007527:Isoenzymes; D019001:Nitric Oxide Synthase