Distinguishing mild cognitive impairment from Alzheimer's disease with acrolein metabolites and creatinine in urine

Clin Chim Acta. 2015 Feb 20:441:115-21. doi: 10.1016/j.cca.2014.12.023. Epub 2014 Dec 24.

Abstract

Background: We previously reported that the level of urinary 3-hydroxypropyl mercapturic acid (3-HPMA)/creatinine (Cre) was reduced following stroke. The aim of this study was to determine whether the level of 3-HPMA/Cre in urine was reduced in subjects with dementia.

Methods: The level of 3-HPMA was measured by LC-MS/MS, and that of amino acid conjugated acrolein (AC-Acro) was by ELISA. The study included 128 elderly subjects divided into 74 non-demented (control), 22 mild cognitive impairment (MCI) and 32 Alzheimer's disease (AD) subjects.

Results: The urinary 3-HPMA/Cre and AC-Acro/Cre in MCI plus AD subjects were significantly lower than those in control subjects. In addition, urinary Cre in AD subjects was significantly higher than that in MCI subjects, and 3-HPMA/Cre and AC-Acro/Cre in AD subjects were significantly lower than that in MCI subjects. Among these three markers, the lower 3-HPMA/Cre ratio was most strongly correlated with the decline of MMSE (Mini-Mental State Examination) and the increase in CDRsob (Clinical Dementia Rating Scale Sum of Boxes Scores). Furthermore, reduction in 3-HPMA/Cre in urine was well correlated with increase in Aβ40/42 in plasma in demented subjects.

Conclusion: The results indicate that 3-HPMA/Cre in urine is the most reliable biochemical marker to distinguish AD subjects from MCI subjects among three markers.

Keywords: 3-HPMA; Acrolein-glutathione metabolite; Alzheimer's disease; Amino acid-conjugated acrolein; Magnetic resonance imaging; Urinary biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / analogs & derivatives
  • Acetylcysteine / urine
  • Acrolein / metabolism*
  • Acrolein / urine*
  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / urine*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / urine*
  • Creatinine / urine*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Middle Aged

Substances

  • Acrolein
  • Creatinine
  • S-(3-hydroxypropyl)cysteine N-acetate
  • Acetylcysteine