Early Candidate Urine Biomarkers for Detecting Alzheimer’s Disease Before Amyloid-β Plaque Deposition in an APP (swe)/PSEN1^dE9 Transgenic Mouse Model

Article type: Research Article

Authors: Zhang, Fanshuang^{a; b; 1} | Wei, Jing^{c; 1} | Li, Xundou^{a; 1} | Ma, Chao^{d; *} | Gao, Youhe^{c; *}

Affiliations: [a] Department of Pathophysiology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China | [b] Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China | [c] Department of Biochemistry and Molecular Biology, Beijing Normal University, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, Beijing, China | [d] Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Neuroscience Center; Joint Laboratory of Anesthesia and Pain, School of Basic Medicine, Peking Union Medical College, Beijing, China

Correspondence: [*] Correspondence to: Youhe Gao, Department of Biochemistry and Molecular Biology, Beijing Normal University, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, Beijing, 100875, China. Tel.: +1 86 10 5880 4382; Fax: +86 10 6521 2284; E-mail: [email protected]. and Chao Ma, Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Neuroscience Center; Joint Laboratory of Anesthesia and Pain, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China. E-mail: [email protected].

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

Abstract: Alzheimer’s disease (AD) is an incurable age-associated neurodegenerative disorder that is characterized by irreversible progressive cognitive deficits and extensive brain damage. The identification of candidate biomarkers before amyloid-β plaque deposition occurs is therefore of great importance for the early intervention of AD. Urine, which is not regulated by homeostatic mechanisms, theoretically accumulates changes associated with AD earlier than cerebrospinal fluid and blood. In this study, an APP (swe)/PSEN1dE9 transgenic mouse model was used to identify candidate biomarkers for early AD. Urine samples were collected from 4-, 6-, and 8-month-old transgenic mouse models, and the urinary proteomes were profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The levels of 29 proteins differed significantly between wild type and 4-month-old mice, which had not started to accumulate amyloid-β plaques. Among these proteins, 13 have been associated with the mechanisms of AD, while 9 have been suggested as AD biomarkers. Our results indicated that urine proteins enable detection of AD before amyloid-β plaque deposition, which may present an opportunity for intervention.

Keywords: Alzheimer’s disease, APP (swe)/PSEN1^dE9, early diagnosis, urine proteome

DOI: 10.3233/JAD-180412

Journal: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 613-637, 2018