UC San Diego

The progression of Alzheimer's disease is theorized to progress from amyloid pathology to tau pathology as shown in the amyloid cascade hypothesis. The pathway for this progression is, as of yet, unknown. Previous studies have shown a correlation between the presence of inducible nitric oxide synthase and the severity of Alzheimer's disease mouse models. Using mice carrying mutations in the amyloid precursor protein crossed with mice lacking inducible nitric oxide synthase we examined the link between disease progression and the presence of nitric oxide synthase. Additionally, mice carrying the amyloid precursor protein (APP) mutation in conjunction with a mutation in the caspase cleavage domain of APP were studied in the context of the ablation of inducible nitric oxide synthase. The mice were evaluated in terms of amyloid plaque load, levels of amyloid beta protein, and levels of hyperphosphorylated tau protein. There was no obvious correlation between the ablation of inducible nitric oxide synthase and the severity of Alzheimer's-like pathology. Mice carrying the caspase cleavage mutation showed a significant increase in amyloid plaque load when completely lacking inducible nitric oxide synthase compared to mice carrying the same mutations but with one copy of the inducible nitric oxide synthase gene