Blood MAPT expression and methylation status in Alzheimer's disease

Abstract

Abstract Aim This study aimed to investigate the expression levels and methylation status of microtubule‐associated protein tau (MAPT) in the blood of Alzheimer's disease (AD) patients and age‐ and sex‐matched healthy controls. Methods Fifty AD outpatients and 50 healthy contorls were enrolled. Blood samples were collected for processing of complementary DNA and genomic DNA. MAPT messenger ribonucleic acid (mRNA) expression was analyzed by real‐time quantitative polymerase chain reaction. The methylation rates of four cytosine‐phosphate‐guanine (CpG) sites in the upstream region of MAPT exon1 were evaluated by the pyrosequencing method. Results No significant differences in MAPT mRNA expression levels were found between AD and control subjects (AD 0.97 ± 0.49 vs. control 1.0 ± 0.64, p = 0.62). MAPT mRNA expression levels were not correlated with any other clinical characteristics or results of psychological tests. MAPT mRNA expression levels were significantly higher in AD subjects treated with acetylcholinesterase inhibitors (AchEIs) (n = 25) than in subjects not treated with AChEIs (n = 25) (unmedicated 0.83 ± 0.33 vs. medicated 1.12 ± 0.59, p = 0.049). The AD subjects did not differ from the control subjects in methylation rates at selected CpG sites. MAPT methylation status were not correlated with clinical characteristics, the results of psychological tests, or MAPT mRNA expression. Conclusion MAPT mRNA expression levels and methylation status in blood do not appear useful as biomarkers for AD or the examined CpG sites were not genetically significant for MAPT gene expression or AD pathology. However, AChEIs may alter MAPT mRNA expression. Further studies are needed to explore blood biomarkers that can discriminate AD patients from controls.

Keywords

• Alzheimer's disease
• blood
• gene expression
• gene methylation
• MAPT