Analysis of HSPA8 and HSPA9 mRNA Expression and Promoter Methylation in the Brain and Blood of Alzheimer's Disease Patients

Article type: Research Article

Authors: Silva, Patricia Natalia^a | Furuya, Tatiane Katsue^a | Braga, Ianna Lacerda^a | Rasmussen, Lucas Trevizani^c | Labio, Roger Willian^c | Bertolucci, Paulo Henrique^b | Chen, Elizabeth Suchi^a | Turecki, Gustavo^d | Mechawar, Naguib^d | Payão, Spencer Luiz^{a; c} | Mill, Jonathan^e | Smith, Marília Cardoso^{a; *}

Affiliations: [a] Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil | [b] Disciplina de Neurologia Clínica, Departamento de Neurologia e Neurocirurgia (UNIFESP), São Paulo, SP, Brazil | [c] Laboratório de Genética, Hemocentro, Faculdade de Medicina de Marília (FAMEMA), Marília, SP, Brazil | [d] Psychiatry Department, Douglas Hospital Research Center, McGill University, Montreal, Canada | [e] Institute of Psychiatry, King's College, London, UK

Correspondence: [*] Correspondence to: Prof. Dr. Marília Cardoso Smith, 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: [email protected].

Abstract: Alzheimer's disease (AD) is the most common form of dementia in elderly. Chaperones may have a crucial role in AD due to their involvement in protein quality control, folding, and degradation. In this study, we investigated the mRNA and promoter DNA methylation levels of two chaperones, HSPA8 and HSPA9, in postmortem brain tissue (entorhinal and auditory cortices and hippocampus) from healthy elderly and AD subjects as well as in peripheral blood of healthy elderly and AD patients. mRNA quantification was performed by qRT-PCR and DNA methylation by mass spectrometry. In the peripheral blood, we did not observe a significant difference in HSPA8 and HSPA9 expression between elderly controls and AD. A significant downregulation of HSPA8 and HSPA9 was observed in AD across the three brain regions compared to the controls, suggesting their participation in AD pathogenesis. However, no important DNA methylation differences were observed, suggesting that other mechanism may be involved in controlling these genes expression.

Keywords: epigenetics, gene expression, HSPA8, HSPA9, mRNA

DOI: 10.3233/JAD-130428

Journal: Journal of Alzheimer's Disease, vol. 38, no. 1, pp. 165-170, 2014