P2–002: Altered arginine metabolism in the Alzheimer's hippocampus

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and neuropathological hallmarks of senile plaques and neurofibrillary tangles, with aging as a major risk factor. L-arginine is a semi-essential amino acid that can be metabolised to produce a number of bioactive metabolites. Accumulating evidence suggests that arginine metabolism may play a prominent role in AD pathogenesis. The present study conducted the enzyme assays, western blot, high-performance liquid chromatography and liquid chromatography mass spectroscopy to compare the L-arginine metabolic profiles in the hippocampus, a brain region that is affected early and severely in AD, in normal cases with an average age of 60 or 80 years and in AD cases with an average age of 80 years. There were AD- and age-related reductions in total activity of nitric oxide synthase (NOS) and protein expression of the constitutive forms of NOS, and AD-related increases in arginase activity and arginase II protein expression. The level of L-ornithine was significantly decreased in the AD group only, with no significant differences between groups in L-arginine and L-citrulline. There were also AD- and age-related changes in putrescine, spermine and glutamate, with no changes in agmatine, spermidine and g -aminobutyric acid. Cluster analyses revealed that the 10 related neurochemical variables formed distinct groups, which changed differentially as a function of advanced aging or AD. These findings demonstrate dramatically altered arginine metabolism in the hippocampus of AD brains, which supports the prominent role of arginine metabolism in AD pathogenesis.