Metabolomic changes in autopsy-confirmed Alzheimer's disease

Rima Kaddurah-Daouk, Steve Rozen, Wayne Matson, Xianlin Han, Christine M. Hulette, James R. Burke, P. Murali Doraiswamy, Kathleen A. Welsh-Bohmer

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)309-317
Number of pages9
JournalAlzheimer's and Dementia
Volume7
Issue number3
DOIs
StatePublished - May 1 2011
Externally publishedYes

Keywords

  • Alzheimer's
  • Biomarkers
  • Diagnosis
  • Metabolomics
  • Purine
  • Staging
  • Tryptophan
  • Tyrosine

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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