Identification of Altered Metabolic Pathways in Plasma and CSF in Mild Cognitive Impairment and Alzheimer's Disease Using Metabolomics

Eugenia Trushina, Tumpa Dutta, Xuan Mai T Persson, Michelle M. Mielke, Ronald C. Petersen

Research output: Contribution to journalArticlepeer-review

243 Scopus citations

Abstract

Alzheimer's Disease (AD) currently affects more than 5 million Americans, with numbers expected to grow dramatically as the population ages. The pathophysiological changes in AD patients begin decades before the onset of dementia, highlighting the urgent need for the development of early diagnostic methods. Compelling data demonstrate that increased levels of amyloid-beta compromise multiple cellular pathways; thus, the investigation of changes in various cellular networks is essential to advance our understanding of early disease mechanisms and to identify novel therapeutic targets. We applied a liquid chromatography/mass spectrometry-based non-targeted metabolomics approach to determine global metabolic changes in plasma and cerebrospinal fluid (CSF) from the same individuals with different AD severity. Metabolic profiling detected a total of significantly altered 342 plasma and 351 CSF metabolites, of which 22% were identified. Based on the changes of >150 metabolites, we found 23 altered canonical pathways in plasma and 20 in CSF in mild cognitive impairment (MCI) vs. cognitively normal (CN) individuals with a false discovery rate

Original languageEnglish (US)
Article numbere63644
JournalPLoS One
Volume8
Issue number5
DOIs
StatePublished - May 20 2013
Externally publishedYes

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine

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