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Changes in methylation patterns of multiple genes from peripheral blood leucocytes of Alzheimer's disease patients

Published online by Cambridge University Press:  21 February 2013

Yaping Hou ,
Huayun Chen ,
Qiong He ,
Wei Jiang ,
Tao Luo ,
Jinhai Duan ,
Nan Mu ,
Yunshao He  and
Huaqiao Wang
Yaping Hou
Affiliation:
Department of Anatomy & Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China
Huayun Chen
Affiliation:
Daan Gene Diagnostic Center, Sun Yat-sen University, Guangzhou, PR China
Qiong He
Affiliation:
Department of Anatomy & Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China
Wei Jiang
Affiliation:
Department of Anatomy & Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China
Tao Luo
Affiliation:
Department of Anatomy & Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China
Jinhai Duan
Affiliation:
East Department of Neurology, Guangdong General Hospital, Guangzhou, PR China Guangdong Academy of Medical Sciences, Guangzhou, PR China Guangdong Institute of Geriatrics, Guangzhou, PR China
Nan Mu
Affiliation:
Guangzhou Brain Hospital, Guangzhou, PR China
Yunshao He
Affiliation:
Daan Gene Diagnostic Center, Sun Yat-sen University, Guangzhou, PR China
Huaqiao Wang*
Affiliation:
Department of Anatomy & Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China
*
Huaqiao Wang, Department of Anatomy & Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, Guangdong province, PR China. Tel: +8602087332218; Fax: +8602084112545; E-mail: whuaqiao@yahoo.com.cn
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Abstract

Background

Efforts aiming at identifying biomarkers and corresponding methods for early diagnosis of Alzheimer's disease (AD) might be the most appropriate strategy to initiate promising new treatments and/or prevention of AD

Objective

The aim of our study is to assess the association of DNA methylation pattern of various leucocyte genes with AD pathogenesis in order to find potential biomarkers and corresponding methods for molecular diagnosis of AD.

Methods

DNA methylation level of various genes in AD patients and normal population were compared by bisulphite sequencing PCR and methylation-specific PCR (MSP). Furthermore, real-time PCR was used to explore the effects of DNA methylation on the expression of target genes.

Results

Results showed significant hypermethylation of mammalian orthologue of Sir2 (SIRT1) gene in AD patients compared with normal population. Meanwhile, changes in methylation level of SIRT1 gene between different severities of AD were also found. Specific primers were designed from the SIRT1 CpG islands to differentiate AD and control group by MSP method. Besides, significant demethylation of β-amyloid precursor protein (APP) gene was observed in AD patients, whereas no difference was observed in other AD-related genes. Moreover, significant decrease in expression of SIRT1 gene and increase in expression of APP gene were also found in AD patients. In addition, the expression level of SIRT1/APP genes was associated with the severity, but not with the age or gender, of AD patients.

Conclusion:SIRT1 and APP might be the interesting candidate biomarkers and valuable for clinical diagnosis or treatment of AD.

Keywords

Alzheimer's diseasebisulphite sequencing PCRDNA methylationSIRT1
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 25 , Issue 2 , April 2013 , pp. 66 - 76
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013

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