Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease

J Exp Med. 1996 Oct 1;184(4):1425-33. doi: 10.1084/jem.184.4.1425.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / pathology
  • Amino Acid Sequence
  • Antibodies, Monoclonal
  • Antibody Specificity
  • Brain / enzymology*
  • Brain / pathology
  • Enzyme Induction
  • Female
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Isoenzymes / isolation & purification*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neurons / enzymology*
  • Neurons / pathology
  • Nitric Oxide Synthase / isolation & purification*

Substances

  • Antibodies, Monoclonal
  • Isoenzymes
  • Nitric Oxide Synthase