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

Abstract

In Alzheimer's disease (AD), affected neurons accumulate β 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 β1 (TGF-β1). Expression of TGF-β1 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 expressed in small amounts in 3 control subjects aged 77-78 years. Thus, human neurons can express NOS2 in vivo. The high-output pathway of NO production may contribute to pathogenesis in AD.