NMR-based metabolomics of urine in a mouse model of Alzheimer’s disease: identification of oxidative stress biomarkers

Fukuhara, Kiyoshi; Ohno, Akiko; Ota, Yosuke; Senoo, Yuya; Maekawa, Keiko; Okuda, Haruhiro; Kurihara, Masaaki; Okuno, Alato; Niida, Shumpei; Saito, Yoshiro; Takikawa, Osamu

doi:10.3164/jcbn.12-118

Cited by 43 publications

(37 citation statements)

References 33 publications

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“…The impaired energy metabolism was also visible when serum samples were subjected to NMR, glucose, citrate, 3-hydroxybutyrate, pyruvate were found to be decreased (Liang et al, 2008). Moreover, analysis on urine samples from APP mice revealed significant metabolic alterations (increased levels of 3-hydroxykynurenine, homogentisate and allantoin) indicative of oxidative stress (Fukuhara et al, 2013).…”

Section: Animal Models Of Admentioning

confidence: 96%

Small molecule biomarkers in Alzheimer’s disease

Kim

Legido‐Quigley

2018

OCL

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-Alzheimer's disease (AD) is a progressive neurodegenerative disease which affects a growing number of people as the population ages worldwide. Alzheimer's Disease International estimated that more than 100 million people will be living with dementia by 2050. At present there are no disease-modifying therapies and research has expanded to the Àomic sciences with scientists aiming to get a holistic view of the disease using systems medicine. Metabolomics and Lipidomics give a snap-shot of the metabolism. As analyzing the brain in vivo is difficult, the metabolic information of the periphery has potential to unravel mechanisms that have not been considered, such as those that link the brain to the liver and the gut or other organs. With that in mind we have produced a mini-review, to record a number of studies in the field and the molecular pathways that have been flagged in animal and human models of AD. Human studies deal with cohorts in the order of the hundreds due to the difficulty of organizing AD studies, however it is possible that these first pilots point towards important mechanisms. The trend in these small studies is the involvement of many organs and pathways. Some findings, that have been reproduced, are ceramides being increased, phospholipids and neurotransmitters depleted and sterols being found depleted too. Initial findings point to an important role to lipid homeostasis in AD, this is not surprising as the brain's main constituents are water and lipids.Keywords: Alzheimer's disease / metabolomics / lipidomics / biomarker Résumé -Biomarqueurs à petites molécules dans la maladie d'Alzheimer. La maladie d'Alzheimer est une maladie neurodégénérative progressive qui affecte un nombre croissant de personnes en raison du vieillissement de la population observé dans le monde entier. La fédération internationale d'associations Alzheimer's disease International estime que plus de 100 millions de personnes vivront avec cette démence d'ici à 2050. Il n'existe actuellement aucun traitement de la maladie et la recherche s'est élargie aux sciences -omiques avec l'objectif scientifique d'obtenir une approche globale de la maladie en utilisant une médecine des systèmes. La métabolomique et la lipidomique donnent un aperçu du métabolisme. L'analyse du cerveau in vivo s'avérant difficile, l'information métabolique de la périphérie possède le potentiel de démêler des mécanismes qui n'ont pas été pris en compte, tels que ceux reliant le cerveau au foie et à l'intestin ou à d'autres organes. Dans cet esprit, nous proposons une mini-revue, afin de lister un certain nombre d'études relevant de ce champ et les voies moléculaires qui ont été signalées chez les modèles animaux et humains de la maladie d'Alzheimer. Les études humaines traitent des cohortes de quelque centaines d'individus en raison de la difficulté à organiser des études sur cette pathologie, mais il est possible que ces premiers pilotes pointent vers des mécanismes importants. La tendance dans ces petites études est l'implication de nombreux org...

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Section: Animal Models Of Admentioning

confidence: 96%

Small molecule biomarkers in Alzheimer’s disease

Kim

Legido‐Quigley

2018

OCL

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“…Because urine is a noninvasive sample animals can be monitored during disease progression. In this sense, urine NMR fingerprints from four control mice and four transgenic APP/tau mice were evaluated at three different time points to represent AD progression states, namely, prior to onset (at 4 months), early-middle progress (at 10 months) and last period of AD (at 15 months) (Fukuhara et al, 2013). Multivariate statistical analysis by means of PCA and OPLS-DA showed a clear discrimination between non-transgenic versus transgenic mice even at onset time point (4 months).…”

Section: Metabolomics Of Neurological Diseases In Other Samplesmentioning

confidence: 99%

Recent Advances and Applications of Metabolomics to Investigate Neurodegenerative Diseases

Ibáñez¹,

Cifuentes²,

Simó³

2015

International Review of Neurobiology

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“…Therefore, urine analyses can detect diseases as different as inflammatory bowel disease (Stephens et al, 2013) and Alzheimer's disease (Fukuhara et al, 2013). PCA3 (prostate cancer gene 3) in urine is the only Food and Drug Administration (FDA)-approved urinary biomarker of clinical PCa, while the fusion gene TMPRSS2 ERG, α-formyl coenzyme A racemic enzyme (AMACR), single nucleotide polymorphism (SNP), and others have also been reported and confirmed to have correlations with PCa.…”

Section: Urinementioning

confidence: 99%

Nuclear magnetic resonance spectroscopy as a new approach for improvement of early diagnosis and risk stratification of prostate cancer

Yang

Lü

Wen

et al. 2017

J. Zhejiang Univ. Sci. B

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Prostate cancer (PCa) is the second most common male cancer worldwide and the fifth leading cause of death from cancer in men. Early detection and risk stratification is the most effective way to improve the survival of PCa patients. Current PCa biomarkers lack sufficient sensitivity and specificity to cancer. Metabolite biomarkers are evolving as a new diagnostic tool. This review is aimed to evaluate the potential of metabolite biomarkers for early detection, risk assessment, and monitoring of PCa. Of the 154 identified publications, 27 and 38 were original papers on urine and serum metabolomics, respectively. Nuclear magnetic resonance (NMR) is a promising method for measuring concentrations of metabolites in complex samples with good reproducibility, high sensitivity, and simple sample processing. Especially urine-based NMR metabolomics has the potential to be a cost-efficient method for the early detection of PCa, risk stratification, and monitoring treatment efficacy.

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NMR-based metabolomics of urine in a mouse model of Alzheimer’s disease: identification of oxidative stress biomarkers

Cited by 43 publications

References 33 publications

Small molecule biomarkers in Alzheimer’s disease

Small molecule biomarkers in Alzheimer’s disease

Recent Advances and Applications of Metabolomics to Investigate Neurodegenerative Diseases

Nuclear magnetic resonance spectroscopy as a new approach for improvement of early diagnosis and risk stratification of prostate cancer

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