TY - JOUR
T1 - SORL1 and SIRT1 mRNA expression and promoter methylation levels in aging and Alzheimer's Disease
AU - Furuya, Tatiane Katsue
AU - Oliveira da Silva, Patricia Natalia
AU - Marques Payao, Spencer Luiz
AU - Rasmussen, Lucas Trevizani
AU - de Labio, Roger Willian
AU - Ferreira Bertolucci, Paulo Henrique
AU - Sampaio Braga, Ianna Lacerda
AU - Chen, Elizabeth Suchi
AU - Turecki, Gustavo
AU - Mechawar, Naguib
AU - Mill, Jonathan
AU - Cardoso Smith, Marilia de Arruda
PY - 2012/12
Y1 - 2012/12
N2 - 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 I) 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.
AB - 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 I) 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.
KW - Alzheimer's Disease
KW - Aging
KW - SORL1 and SIRT1 mRNA expression
KW - Peripheral blood leukocytes
KW - Post mortem brain tissue
KW - Promoter DNA methylation
KW - RECEPTOR LR11
U2 - 10.1016/j.neuint.2012.07.014
DO - 10.1016/j.neuint.2012.07.014
M3 - Article
SN - 0197-0186
VL - 61
SP - 973
EP - 975
JO - Neurochemistry International
JF - Neurochemistry International
IS - 7
M1 - N/A
ER -