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

Acta Neuropsychiatr. 2013 Apr;25(2):66-76. doi: 10.1111/j.1601-5215.2012.00662.x.


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.