SORL1 and SIRT1 mRNA expression and promoter methylation levels in aging and Alzheimeras Disease

• Published in: Neurochemistry international Vol. 61; no. 7; pp. 973 - 975
• Main Authors: Furuya, Tatiane Katsue, da Silva, Patricia Natalia Oliveira, Payao, Spencer Luiz Marques, Rasmussen, Lucas Trevizani, de Labio, Roger Willian, Bertolucci, Paulo Henrique Ferreira, Braga, Ianna Lacerda Sampaio, Chen, Elizabeth Suchi, Turecki, Gustavo, Mechawar, Naguib, Mill, Jonathan, de Arruda Cardoso Smith, Marilia
• Format: Journal Article
• Language: English
• Published: 01-12-2012
• Subjects: Aging; Alzheimer's disease; Brain; Dementia disorders; DNA methylation; epigenetics; Gene expression; Geriatrics; Hippocampus; Leukocytes; Mass spectroscopy; Neurodegenerative diseases; Peripheral blood; Polymerase chain reaction; SIRT1 protein; Sirtuins
• ISSN: 0197-0186
• DOI: 10.1016/j.neuint.2012.07.014

Alzheimeras 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.