Rapid communication SORL1 and SIRT1 mRNA expression and promoter methylation levels in aging and Alzheimer’s Disease Tatiane Katsue Furuya a , Patrícia Natália Oliveira da Silva a , Spencer Luiz Marques Payão a,b,f , Lucas Trevizani Rasmussen f , Roger Willian de Labio b , Paulo Henrique Ferreira Bertolucci c , Ianna Lacerda Sampaio Braga a , Elizabeth Suchi Chen a , Gustavo Turecki d , Naguib Mechawar d , Jonathan Mill e , Marília de Arruda Cardoso Smith a,⇑ a Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo-SP, Brazil b Laboratório de Genética, Hemocentro, Faculdade de Medicina de Marília (FAMEMA), Marília-SP, Brazil c Disciplina de Neurologia Clínica, Departamento de Neurologia e Neurocirurgia (UNIFESP), São Paulo-SP, Brazil d Psychiatry Department, Douglas Hospital Research Center, McGill University, Montreal, Canada e Institute of Psychiatry, King’s College, London, United Kingdom f Pró-Reitoria de Pesquisa e Pós-graduação, Universidade Sagrado Coração (USC), Bauru-SP, Brazil article info Article history: Received 2 June 2012 Received in revised form 7 July 2012 Accepted 13 July 2012 Available online 23 July 2012 Keywords: Alzheimer’s Disease Aging SORL1 and SIRT1 mRNA expression Peripheral blood leukocytes Post mortem brain tissue Promoter DNA methylation 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 pro- moter 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 leuko- cytes 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. Further- more, 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. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Alzheimer’s Disease (AD) is the most common cause of demen- tia and its prevalence increases exponentially with age. It is a het- erogeneous disorder and the cause of the sporadic form is still unknown, probably caused by a complex interaction among aging, several susceptibility genes and environmental risk factors (Blen- now et al., 2006). Moreover, the epigenetic variability could affect the AD predisposition and the course of the disease in addition to these factors (Wang et al., 2008). Some findings have linked the lipoprotein receptor SORL1 (sor- tilin-related receptor; also known as LR11 or SorLA) to AD patho- genesis, based on its reduction in AD brains and its ability to lower Amyloid b (Ab) levels, one of the hallmarks of this disease. SORL1 is known to bind to apolipoprotein E (APOE), the main lipo- protein expressed in the brain. Furthermore, APOE e4 allele is one of the main genetic risk factor associated to the sporadic form of AD (Offe et al., 2006). Another important molecule that has been implicated in the pathogenesis of AD is SIRT1 (sirtuin 1), member of the sirtuins fam- ily, which are protein deacetylases, essential for the regulation of various cellular functions. SIRT1 might regulate aging and meta- bolic processes involved in AD and its loss has been associated with the disease progression (Julien et al., 2009). Furthermore, SIRT1 0197-0186/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neuint.2012.07.014 Abbreviations: ACTB, actin beta; AD, Alzheimer’s Disease; Ab, Amyloid b; APOE, apolipoprotein E; CDR, Clinical Dementia Rating; df, degrees of freedom; DSM-IV, IV Diagnostic and Statistical Manual of Mental Disorders; GLM, General Linear Model; N, number of individuals; NINCDS-ADRDA, National Institute of Neurological and Communicative Disorders and Stroke – Alzheimer’s Disease and Related Disorders Association; MMSE, Mini-Mental State Examination; qRT-PCR, quantitative Reverse Transcription Polymerase Chain Reaction; RQ, relative quantification; SD, Standard deviation; SIRT1, sirtuin 1; SORL1, sortilin-related receptor. ⇑ Corresponding author. Address: Disciplina de Genética, Departamento de Morfologia e Genética, UNIFESP/EPM Rua Botucatu, 740, Edifício Leitão da Cunha –1° andar, CEP 04023-900 São Paulo/SP, Brazil. Tel.: +55 11 5576 4260; fax: +55 11 5576 4264. E-mail address: tuty_furuya@yahoo.com.br (M. de Arruda Cardoso Smith). Neurochemistry International 61 (2012) 973–975 Contents lists available at SciVerse ScienceDirect Neurochemistry International journal homepage: www.elsevier.com/locate/nci