INDUCIBLE NITRIC-OXIDE SYNTHASE IN TANGLE-BEARING NEURONS OF PATIENTSWITH ALZHEIMERS-DISEASE

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. Product s of NOS2 can be neurotoxic. In mice, NOS2 is normally suppressed by t ransforming growth factor beta 1 (TGF-beta 1). Expression of TGF-beta 1 is decreased in brains from AD patients, a situation that might be p ermissive for accumulation of NOS2. Accordingly, we investigated the e xpression of NOS2 in patients with AD, using three monospecific antibo dies: a previously described polyclonal and two new monoclonal antibod ies. Neurofibrillary tangle-bearing neurons and neuropil threads conta ined 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 subj ects aged 77-87 years. Thus, human neurons can express NOS2 in vivo. T he high-output pathway of NO production may contribute to pathogenesis in AD.