SORL1 and SIRT1 mRNA expression and promoter methylation levels in aging and Alzheimer’s Disease |
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| Authors: | Tatiane Katsue Furuya Patrícia Natália Oliveira da Silva Spencer Luiz Marques Payão Lucas Trevizani Rasmussen Roger Willian de Labio Paulo Henrique Ferreira Bertolucci Ianna Lacerda Sampaio Braga Elizabeth Suchi Chen Gustavo Turecki Naguib Mechawar Jonathan Mill Marília de Arruda Cardoso Smith |
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| Institution: | 1. Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo-SP, Brazil;2. Laboratório de Genética, Hemocentro, Faculdade de Medicina de Marília (FAMEMA), Marília-SP, Brazil;3. Disciplina de Neurologia Clínica, Departamento de Neurologia e Neurocirurgia (UNIFESP), São Paulo-SP, Brazil;4. Psychiatry Department, Douglas Hospital Research Center, McGill University, Montreal, Canada;5. Institute of Psychiatry, King’s College, London, United Kingdom;6. Pró-Reitoria de Pesquisa e Pós-graduação, Universidade Sagrado Coração (USC), Bauru-SP, Brazil |
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| Abstract: | Alzheimer’s Disease (AD) is a neurodegenerative disorder and the most common cause of dementia among the elderly. Efforts have been made to understand the genetic and epigenetic mechanisms involved in the development of this disease. As SORL1 (sortilin-related receptor) and SIRT1 (sirtuin 1) genes have been linked to AD pathogenesis, we aimed to investigate their mRNA expression and promoter DNA methylation in post mortem brain tissues (entorhinal and auditory cortices and hippocampus) from healthy elderly subjects and AD patients. We also evaluated these levels in peripheral blood leukocytes from young, healthy elderly and AD patients, investigating whether there was an effect of age on these profiles. The comparative CT method by Real Time PCR and MALDI-TOF mass spectrometry were used to analyze gene expression and DNA methylation, respectively. SORL1 gene was differently expressed in the peripheral blood leukocytes and might act as a marker of aging in this tissue. Furthermore, we found that SORL1 promoter DNA methylation might act as one of the mechanisms responsible for the differences in expression observed between blood and brain for both healthy elderly and AD patients groups. The impact of these studied genes on AD pathogenesis remains to be better clarified. |
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