Urinary Amino Acid-Conjugated Acrolein and Taurine as New Biomarkers for Detection of Dementia

Article type: Research Article

Authors: Yoshida, Madoka^{a; 1} | Uemura, Takeshi^{a; b; 1; 2} | Mizoi, Mutsumi^a | Waragai, Masaaki^c | Sakamoto, Akihiko^d | Terui, Yusuke^d | Kashiwagi, Keiko^d | Igarashi, Kazuei^{a; b; *}

Affiliations: [a] Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan | [b] Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan | [c] Higashi-Matsudo Municipal Hospital, Matsudo, Chiba, Japan | [d] Faculty of Pharmacy, Chiba Institute of Science, Choshi, Chiba, Japan

Correspondence: [*] Correspondence to: Dr. Kazuei Igarashi, Amine Pharma Research Institute, Innovation Plaza at Chiba University, 1-8-15 Inohana, Chuo-ku, Chiba, Chiba 260-0856, Japan. Tel.: +81 43 224 7500; E-mail: [email protected].

Note: [1] These authors equally contributed to this work.

Note: [2] Present address: Department of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan

Abstract: Background:Dementia, including Alzheimer’s disease (AD), is one of the serious diseases at advanced age, and its early detection is important for maintaining quality of life (QOL). Objective:In this study, we sought novel biomarkers for dementia in urine. Methods:Samples of urine were collected from 57 control subjects without dementia, 62 mild cognitive impairment (MCI) patients, and 42 AD patients. Mini-Mental State Examination (MMSE) was evaluated when subjects were examined by medical doctors. Urinary amino acid (lysine)-conjugated acrolein (AC-Acro) was measured using N ɛ-(3-formyl-3, 4-dehydropiperidine) lysine (FDP-Lys) ELISA kit, and taurine content was measured using a taurine assay kit. Values were normalized by creatinine content which was measured with the colorimetric assay kit. Results:We found that urinary amino acid (lysine)-conjugated acrolein (AC-Acro) and taurine negatively correlated with MMSE score and are significantly lower in dementia patients compared to the normal subjects. When AC-Acro and taurine were evaluated together with age using an artificial neural network model, median relative risk values for subjects with AD, subjects with mild cognitive impairment, and control subjects were 0.96, 0.53, and 0.06, respectively. Conclusion:Since urine is relatively easy to collect, our findings provide a novel biomarker for dementia without invasiveness.

Keywords: Alzheimer’s disease, amino acid-conjugated acrolein (AC-Acro), Mini-Mental State Examination, taurine, urinary biomarkers

DOI: 10.3233/JAD-220912

Journal: Journal of Alzheimer's Disease, vol. 92, no. 1, pp. 361-369, 2023