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

• Urinary 3-HPMA/Cre in AD subjects was lower than that in MCI subjects.
• The lower 3-HPMA/Cre ratio was well correlated with MMSE.
• The reduction in 3-HPMA/Cre was correlated with the increase in Aβ40/42 in plasma.
• 3-HPMA/Cre ratio is a reliable marker to distinguish AD subjects from MCI subjects.

BackgroundWe 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.MethodsThe 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.ResultsThe 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.ConclusionThe results indicate that 3-HPMA/Cre in urine is the most reliable biochemical marker to distinguish AD subjects from MCI subjects among three markers.