BACKGROUND: Metabolomics, the global science of biochemistry, provides powerful tools to map perturbations in the metabolic network and enables simultaneous quantification of several metabolites to identify metabolic perturbances that might provide insights into disease. METHODS: In this pilot study, we took a targeted electrochemistry-based metabolomics approach where liquid chromatography followed by coulometric array detection enables quantification of over 30 metabolites within key neurotransmitter pathways (dopamine and serotonin) and pathways involved in oxidative stress. RESULTS: Using samples from postmortem ventricular cerebrospinal fluid (15 Alzheimer's disease [AD] and 15 nondemented subjects with autopsy-confirmed diagnoses) and by using regression models, correlations, Wilcoxon rank-sum tests, and t-tests we identified alterations in tyrosine, tryptophan, purine, and tocopherol pathways in patients with AD. Reductions in norepinephrine and its related metabolites were also seen, consistent with previously published data. CONCLUSIONS: These data support further investigation of metabolomics in larger samples of clinical AD as well as in those with preclinical disease for use as biomarkers.
BACKGROUND: Metabolomics, the global science of biochemistry, provides powerful tools to map perturbations in the metabolic network and enables simultaneous quantification of several metabolites to identify metabolic perturbances that might provide insights into disease. METHODS: In this pilot study, we took a targeted electrochemistry-based metabolomics approach where liquid chromatography followed by coulometric array detection enables quantification of over 30 metabolites within key neurotransmitter pathways (dopamine and serotonin) and pathways involved in oxidative stress. RESULTS: Using samples from postmortem ventricular cerebrospinal fluid (15 Alzheimer's disease [AD] and 15 nondemented subjects with autopsy-confirmed diagnoses) and by using regression models, correlations, Wilcoxon rank-sum tests, and t-tests we identified alterations in tyrosine, tryptophan, purine, and tocopherol pathways in patients with AD. Reductions in norepinephrine and its related metabolites were also seen, consistent with previously published data. CONCLUSIONS: These data support further investigation of metabolomics in larger samples of clinical AD as well as in those with preclinical disease for use as biomarkers.
Authors: Steve Rozen; Merit E Cudkowicz; Mikhail Bogdanov; Wayne R Matson; Bruce S Kristal; Chris Beecher; Scott Harrison; Paul Vouros; Jimmy Flarakos; Karen Vigneau-Callahan; Theodore D Matson; Kristyn M Newhall; M Flint Beal; Robert H Brown; Rima Kaddurah-Daouk Journal: Metabolomics Date: 2005 Impact factor: 4.290
Authors: Leslie M Shaw; Hugo Vanderstichele; Malgorzata Knapik-Czajka; Christopher M Clark; Paul S Aisen; Ronald C Petersen; Kaj Blennow; Holly Soares; Adam Simon; Piotr Lewczuk; Robert Dean; Eric Siemers; William Potter; Virginia M-Y Lee; John Q Trojanowski Journal: Ann Neurol Date: 2009-04 Impact factor: 10.422
Authors: Vincent Chouraki; Sarah R Preis; Qiong Yang; Alexa Beiser; Shuo Li; Martin G Larson; Galit Weinstein; Thomas J Wang; Robert E Gerszten; Ramachandran S Vasan; Sudha Seshadri Journal: Alzheimers Dement Date: 2017-06-08 Impact factor: 21.566
Authors: Ben Readhead; Jean-Vianney Haure-Mirande; Cory C Funk; Matthew A Richards; Paul Shannon; Vahram Haroutunian; Mary Sano; Winnie S Liang; Noam D Beckmann; Nathan D Price; Eric M Reiman; Eric E Schadt; Michelle E Ehrlich; Sam Gandy; Joel T Dudley Journal: Neuron Date: 2018-06-21 Impact factor: 17.173
Authors: AmanPreet Badhwar; G Peggy McFall; Shraddha Sapkota; Sandra E Black; Howard Chertkow; Simon Duchesne; Mario Masellis; Liang Li; Roger A Dixon; Pierre Bellec Journal: Brain Date: 2020-05-01 Impact factor: 13.501