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Analysis of SNAP25 mRNA expression and promoter DNA methylation in brain areas of Alzheimer’s Disease patients

2012; Elsevier BV; Volume: 220; Linguagem: Inglês

10.1016/j.neuroscience.2012.06.035

1873-7544

Tatiane Katsue Furuya, Patrícia Natália Silva, Spencer L. M. Payão, Paulo Henrique Ferreira Bertolucci, Lucas Trevizani Rasmussen, Roger Willian de Lábio, Ianna Lacerda Sampaio Braga, Elizabeth Chen, Gustavo Turecki, Naguib Mechawar, Jonathan Mill, Marı́lia de Arruda Cardoso Smith,

Genetics and Neurodevelopmental Disorders

Abstract Alzheimer′s Disease (AD) is the most common cause of dementia in elderly people. The presynaptic terminal is an important site of pathological changes in AD, leading to synaptic loss in specific brain regions, such as in the cortex and hippocampus. In this study, we investigated synaptosomal-associated protein, 25-kDa ( SNAP25 ) mRNA levels and promoter DNA methylation in post mortem brain tissues (entorhinal and auditory cortices and hippocampus) from healthy elderly and AD subjects as well as in peripheral blood leukocytes of young, healthy elderly and AD patients. mRNA quantification was performed by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) using the ΔΔ C T method and promoter DNA methylation was quantified by mass spectrometry using the Sequenom EpiTYPER platform. We observed a significant decrease in SNAP25 expression in AD across all the three brain regions in relation to the healthy elderly subjects, suggesting impairment in synaptic function. The changes in the auditory cortex reflected those observed in the hippocampus and entorhinal cortex, the primary areas affected in AD. However, no AD-associated differences in SNAP25 promoter DNA methylation were observed suggesting that other mechanisms may be involved in mediating the observed gene expression changes.