title: SORL1 and SIRT1 mRNA expression and promoter methylation levels in aging and Alzheimer's Disease.
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.
authors: Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo-SP, Brazil. tuty_furuya@yahoo.com.br
authors: Tatiane Katsue
authors: TK
authors: Furuya
authors: Patrícia Natália Oliveira
authors: PN
authors: da Silva
authors: Spencer Luiz Marques
authors: SL
authors: Payão
authors: Lucas Trevizani
authors: LT
authors: Rasmussen
authors: Roger Willian
authors: RW
authors: de Labio
authors: Paulo Henrique Ferreira
authors: PH
authors: Bertolucci
authors: Ianna Lacerda Sampaio
authors: IL
authors: Braga
authors: Elizabeth Suchi
authors: ES
authors: Chen
authors: Gustavo
authors: G
authors: Turecki
authors: Naguib
authors: N
authors: Mechawar
authors: Jonathan
authors: J
authors: Mill
authors: Marília
authors: M
authors: de Arruda Cardoso Smith
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C102582:SORL1 protein, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1