title: NMR-based metabolomics of urine in a mouse model of Alzheimer's disease: identification of oxidative stress biomarkers.
abstract: Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia among elderly patients. A biomarker for the disease could make diagnosis easier and more accurate, and accelerate drug discovery. In this study, NMR-based metabolomics analysis in conjunction with multivariate statistics was applied to examine changes in urinary metabolites in transgenic AD mice expressing mutant tau and β-amyloid precursor protein. These mice showed significant changes in urinary metabolites throughout the progress of the disease. Levels of 3-hydroxykynurenine, homogentisate and allantoin were significantly higher compared to control mice in 4 months (prior to onset of AD symptoms) and reverted to control values by 10 months of age (early/middle stage of AD), which highlights the relevance of oxidative stress to this neurodegenerative disorder even prior the onset of dementia. The level of these changed metabolites at very early period may provide an indication of disease risk at asymptomatic stage.
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fukuhara
authors.forename: Akiko
authors.initials: A
authors.lastname: Ohno
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ota
authors.forename: Yuya
authors.initials: Y
authors.lastname: Senoo
authors.forename: Keiko
authors.initials: K
authors.lastname: Maekawa
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Okuda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kurihara
authors.forename: Alato
authors.initials: A
authors.lastname: Okuno
authors.forename: Shumpei
authors.initials: S
authors.lastname: Niida
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Osamu
authors.initials: O
authors.lastname: Takikawa
keywords: Alzheimer’s disease; NMR; biomarker; metabolomics; oxidative stress