The pattern of NADPH-diaphorase staining, a marker of nitric oxide synthase activity, is altered in the perforant pathway terminal zone in Alzheimer's disease.

NADPH-diaphorase positive neurons are relatively spared in Alzheimer's disease (AD). We show here, however, that the pattern of NADPH-diaphorase staining in the neuropil of the hippocampus changes dramatically in the brains of patients with AD. Control individuals displayed a striking band of NADPH-diaphorase staining in the middle 1/3 of the molecular layer of the dentate gyrus; this band was absent in AD. Staining in the molecular layer was reduced 18-31% in AD (P < 0.001) with the greatest loss in the most severely affected cases. NADPH diaphorase is thought to reflect the presence of nitric oxide synthase. Because nitric oxide has been implicated in long-term potentiation, changes in its expression could reflect loss of synapses important for memory formation.