Altered arginine metabolism in Alzheimer's disease brains.

L-arginine is a semi-essential amino acid with a number of bioactive metabolites. Accumulating evidence suggests the implication of altered arginine metabolism in the pathogenesis of Alzheimer's disease (AD). The present study systematically compared the metabolic profile of L-arginine in the superior frontal gyrus, hippocampus, and cerebellum from AD (mean age 80 years) and normal (mean age 80 or 60 years) cases. The activity and protein expression of nitric oxide synthase and arginase were altered with AD and age in a region-specific manner. There were also AD- and age-related changes in the tissue concentrations of L-arginine and its downstream metabolites (L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine, glutamate, γ-aminobutyric acid, and glutamine) in a metabolite- or region-specific manner. These findings demonstrate that arginine metabolism is dramatically altered in diverse regions of AD brains, thus meriting further investigation to understand its role in the pathogenesis and/or progression of the disease.