Proteomic Analysis of Serum Proteins in Triple Transgenic Alzheimer's Disease Mice: Implications for Identifying Biomarkers for Use to Screen Potential Candidate Therapeutic Drugs for Early Alzheimer's Disease
Affiliations: [a] State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Changchun, P.R. China | [b] Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China | [c] University of Chinese Academy of Sciences, Beijing, China | [d] College of Life Sciences, Shenzhen University, Shenzhen, China
Correspondence:
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Correspondence to: Dr. Xifei Yang and Jianjun Liu, No 8 Longyuan Road, Nanshan District, Shenzhen 518055, Guangdong, China. Tel.: +86 755 25601914; Fax: +86 755 25508584; E-mail: xifeiyang@gmail.com (Xifei Yang); Tel./Fax: +86 755 25508584; E-mail: junii8@126.com (Jianjun Liu).
Abstract: Alzheimer's disease (AD) is the most common fatal neurodegenerative disease affecting the elderly worldwide. There is an urgent need to identify novel biomarkers of early AD. This study aims to search for potential early protein biomarkers in serum from a triple transgenic (PS1M146V/APPSwe/TauP301L) mouse model. Proteomic analysis via two-dimensional fluorescence difference gel electrophoresis was performed on serum samples from wild-type (WT) and triple transgenic mice that were treated with or without coenzyme Q10 (CoQ10) (800 mg/kg body weight/day), a powerful endogenous antioxidant displaying therapeutic benefits against AD pathology and cognitive impairment in multiple AD mouse models, for a period of three months beginning at two months of age. A total of 15 differentially expressed serum proteins were identified between the WT and AD transgenic mice. The administration of CoQ10 was found to alter the changes in the differentially expressed serum proteins by upregulating 10 proteins and down-regulating 10 proteins. Among the proteins modulated by CoQ10, clusterin and α-2-macroglobulin were validated via ELISA assay. These findings revealed significant changes in serum proteins in the AD mouse model at an early pathological stage and demonstrated that administration of CoQ10 could modulate these changes in serum proteins. Our study suggested that these differentially expressed serum proteins could serve as potential protein biomarkers of early AD and that screening for potential candidate AD therapeutic drugs and monitoring of therapeutic effects could be performed via measurement of the changes in these differentially expressed serum proteins.
