Metabolomic changes in autopsy-confirmed Alzheimer's disease

Alzheimers Dement. 2011 May;7(3):309-17. doi: 10.1016/j.jalz.2010.06.001. Epub 2010 Nov 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / metabolism*
  • Autopsy
  • Biogenic Amines / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Biomarkers / metabolism
  • Electrochemical Techniques / methods
  • Female
  • Humans
  • Male
  • Metabolomics / methods*
  • Oxidative Stress / physiology
  • Pilot Projects
  • Predictive Value of Tests
  • Purines / cerebrospinal fluid
  • Tocopherols / cerebrospinal fluid

Substances

  • Biogenic Amines
  • Biomarkers
  • Purines
  • Tocopherols