Unbiased Metabolomic Investigation of Alzheimer's Disease Brain Points to Dysregulation of Mitochondrial Aspartate Metabolism

Giuseppe Paglia, Matteo Stocchero, Stefano Cacciatore, Steven Lai, Peggi Angel, Mohammad Tauqeer Alam, Markus Keller, Markus Ralser, Giuseppe Astarita

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is the most common cause of adult dementia. Yet the complete set of molecular changes accompanying this inexorable, neurodegenerative disease remains elusive. Here we adopted an unbiased lipidomics and metabolomics approach to surveying frozen frontal cortex samples from clinically characterized AD patients (n = 21) and age-matched controls (n = 19), revealing marked molecular differences between them. Then, by means of metabolomic pathway analysis, we incorporated the novel molecular information into the known biochemical pathways and compared it with the results of a metabolomics meta-analysis of previously published AD research. We found six metabolic pathways of the central metabolism as well as glycerophospholipid metabolism predominantly altered in AD brains. Using targeted metabolomics approaches and MS imaging, we confirmed a marked dysregulation of mitochondrial aspartate metabolism. The altered metabolic pathways were further integrated with clinical data, showing various degrees of correlation with parameters of dementia and AD pathology. Our study highlights specific, altered biochemical pathways in the brains of individuals with AD compared with those of control subjects, emphasizing dysregulation of mitochondrial aspartate metabolism and supporting future venues of investigation.

Original languageEnglish
Pages (from-to)608-618
Number of pages11
JournalJournal of Proteome Research
Volume15
Issue number2
DOIs
Publication statusPublished - Feb 5 2016
Externally publishedYes

Keywords

  • Alzheimer's disease
  • lipidomics
  • lipids
  • metabolic pathways
  • metabolomics

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry

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