NOS2 and Alzheimer disease: Purified NOS directly catalyzes the generation of oxygen radicals.23 NOS is upregulated in patients with AD, suggesting that these enzymes are instrumental in the pathogenesis of this disease.24 Cigarette smoking has been associated with increased production of reactive oxygen species,25,26 stimulating pro-inflammatory gene transcription and the release of cytokines, such as tumor necrosis factor α (TNFα), which is associated with further increases in Aβ formation.27,28