title: Distinguishing mild cognitive impairment from Alzheimer's disease with acrolein metabolites and creatinine in urine.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Higashi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Kyoshiro
authors.initials: K
authors.lastname: Kuni
authors.affiliation: Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Mizoi
authors.affiliation: Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Saiki
authors.affiliation: Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Higashi-Matsudo Municipal Hospital, Matsudo, Chiba, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Waragai
authors.affiliation: Higashi-Matsudo Municipal Hospital, Matsudo, Chiba, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Uemura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toida
authors.affiliation: Faculty of Pharmacy, Chiba Institute of Science, Choshi, Chiba, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kashiwagi
authors.affiliation: Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan. Electronic address: iga16077@faculty.chiba-u.jp.
authors.forename: Kazuei
authors.initials: K
authors.lastname: Igarashi
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000652:urine; D000171:Acrolein / Q000378:metabolism* / Q000652:urine*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000652:urine*; D060825:Cognitive Dysfunction / Q000378:metabolism / Q000652:urine*; D003404:Creatinine / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000171:Acrolein; D003404:Creatinine; C001423:S-(3-hydroxypropyl)cysteine N-acetate; D000111:Acetylcysteine
keywords: 3-HPMA; Acrolein-glutathione metabolite; Alzheimer's disease; Amino acid-conjugated acrolein; Magnetic resonance imaging; Urinary biomarker