title: Altered arginine metabolism in Alzheimer's disease brains.
abstract: 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.
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand. Electronic address: ping.liu@otago.ac.nz.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Fleete
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: Nicola D
authors.initials: ND
authors.lastname: Collie
authors.affiliation: Centre for Brain Research and Department of Anatomy with Radiology, University of Auckland, New Zealand.
authors.forename: Maurice A
authors.initials: MA
authors.lastname: Curtis
authors.affiliation: Centre for Brain Research and Department of Anatomy with Radiology, University of Auckland, New Zealand.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Waldvogel
authors.affiliation: Centre for Brain Research and Department of Anatomy with Radiology, University of Auckland, New Zealand.
authors.forename: Richard L M
authors.initials: RL
authors.lastname: Faull
authors.affiliation: Brain Health Research Centre, University of Otago, Dunedin, New Zealand; Department of Psychology, University of Otago, Dunedin, New Zealand.
authors.forename: Wickliffe C
authors.initials: WC
authors.lastname: Abraham
authors.affiliation: Brain Health Research Centre, University of Otago, Dunedin, New Zealand; School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism*; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D002531:Cerebellum / Q000201:enzymology / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009928:Organ Specificity; D017397:Prefrontal Cortex / Q000201:enzymology / Q000378:metabolism*
chemical_list: D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase
keywords: Aging; Alzheimer's disease; Arginase; Nitric oxide synthase; Polyamines; Urea cycle