Madoka Yoshida1, Kyohei Higashi2, Kyoshiro Kuni2, Mutsumi Mizoi1, Ryotaro Saiki3, Mizuho Nakamura1, Masaaki Waragai4, Kenichi Uemura4, Toshihiko Toida2, Keiko Kashiwagi5, Kazuei Igarashi6. 1. Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan. 2. Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan. 3. Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan. 4. Higashi-Matsudo Municipal Hospital, Matsudo, Chiba, Japan. 5. Faculty of Pharmacy, Chiba Institute of Science, Choshi, Chiba, Japan. 6. 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.
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.
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.
Authors: Carolina P Bernardes; Neife A G Santos; Tassia R Costa; Flavia Sisti; Lilian Amaral; Danilo L Menaldo; Martin K Amstalden; Diego L Ribeiro; Lusânia M G Antunes; Suely Vilela Sampaio; Antonio C Santos Journal: Neurotox Res Date: 2019-10-25 Impact factor: 3.911