Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease subjects

Amino Acids. 2007 Feb;32(2):213-24. doi: 10.1007/s00726-006-0409-8. Epub 2006 Oct 10.

Abstract

Our aim was to determine changes in free amino acid (FAA) and dipeptide (DP) concentrations in probable Alzheimer's disease (pAD) subjects compared with control (CT) subjects using liquid chromatography and electrospray ionization tandem mass spectrometry (LCMS2). We recruited gender- and age-matched study participants based on neurological and neuropsychological assessments. We measured FAAs and DPs in cerebrospinal fluid (CSF), plasma and urine using LCMS2 with selected reaction monitoring (SRM). Imidazole-containing FAAs (histidine, methyl-histidine), catecholamines (L-DOPA and dopamine), citrulline, ornithine, glycine and antioxidant DPs (carnosine and anserine) accounted for the major changes between CT and pAD. Carnosine levels were significantly lower in pAD (328.4 +/- 91.31 nmol/dl) than in CT plasma (654.23 +/- 100.61 nmol/dl). In contrast, L-DOPA levels were higher in pAD (1400.84 +/- 253.68) than CT (513.10 +/- 121.61 nmol/dl) plasma. These data underscore the importance of FAA and DP metabolism in the pathogenesis of AD. Since our data show changes in antioxidants, neurotransmitters and their precursors, or FAA associated with urea metabolism in pAD compared with CT, we propose that manipulation of these metabolic pathways may be important in preventing AD progression.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / urine*
  • Amino Acids / blood*
  • Amino Acids / cerebrospinal fluid*
  • Amino Acids / urine*
  • Antioxidants / chemistry
  • Carnosine / analysis
  • Chromatography, Liquid
  • Dipeptides / blood*
  • Dipeptides / cerebrospinal fluid*
  • Dipeptides / urine*
  • Disease Progression
  • Female
  • Histidine / chemistry
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Amino Acids
  • Antioxidants
  • Dipeptides
  • Histidine
  • Carnosine