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Positive association of a Sirt1 variant and parameters of oxidative stress on Alzheimer’s disease

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Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disorder and the most common type of dementia in the elderly. Although its cause is not completely known, several studies suggest that oxidative stress plays an important role in the etiology of this disease. The SIRT1 and SOD2 proteins are linked to pathways that may impair oxidative stress. In this study, we analyzed the association between polymorphisms in these genes and in the APOE gene, through RT-PCR, as well as between environmental factors and the risk of AD. Additionally, the thiobarbituric acid reactive substance assay was performed to estimate the plasma level of malondialdehyde (MDA), a biomarker of lipid peroxidation. Furthermore, some cytogenetic studies indicate that cells of AD patients show increased chromosomal damage; thus, we performed the micronucleus cytome assay to assess cytogenetic damage in AD patients. As expected, the APOE polymorphisms were found to be highly associated with AD. Additionally, the CT genotype of the SIRT1 gene showed a positive association with the disease. The frequencies of genomic damage (micronucleus, buds, nucleoplasmic bridges and binucleated cells), the presence of cell death biomarkers (condensed chromatin, karyorrhexis and pyknosis), and the plasma level of MDA were significantly greater in AD patients than in controls. Our results support the hypothesis that AD is a condition with increased oxidative stress and genomic instability, which may contribute to the neurodegeneration in AD.

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Funding

This study was supported by Fundo de Apoio à Ciência e Tecnologia do Município de Vitória (grant number 5928/2011), Fundação de Amparo à Pesquisa do Estado do Espírito Santo, Programa de Pesquisa para o Sistema Único de Saúde (grant number 65849124), Ministério da Ciência, Tecnologia e Inovação, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Ministério da Educação, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (grant number 552672/2011–4).

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Authors and Affiliations

  1. Programa de Pós-Graduação em Biotecnologia, Renorbio, Universidade Federal do Espírito Santo, CEP, Vitória, ES, 29043-900, Brazil

    Daniela Camporez, Jucimara Ferreira Figueiredo Almeida & Flavia de Paula

  2. Departamento de Ciências Biológicas, Centro de Ciências Humanas e Naturais, Universidade Federal do Espírito Santo, Av. Fernando Ferrari, 514, Goiabeiras, Prédio Lydia Behar, sl. 102, Vitória, ES, CEP 29075-910, Brazil

    Daniela Camporez, Jucimara Ferreira Figueiredo Almeida, Maria do Carmo Pimentel Batitucci & Flavia de Paula

  3. Instituto Federal de Educação, Ciência e Tecnologia do Rio Grande do Sul, Viamão, RS, Brazil

    Luciano Belcavello

  4. Departamento de Educação Integrada em Saúde, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES, CEP 29043-900, Brazil

    Geralda Gillian Silva-Sena

  5. Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória, Vitória, ES, CEP 29027-502, Brazil

    Lúcia Helena Sagrillo Pimassoni & Renato Lírio Morelato

  6. Hospital da Santa Casa de Misericórdia de Vitória, Vitória, ES, CEP 29025-023, Brazil

    Renato Lírio Morelato

  7. Programa de Pós-Graduação em Biologia Vegetal, Centro de Ciências Humanas e Naturais, Universidade Federal do Espírito Santo, Vitória, ES, CEP 29075-910, Brazil

    Maria do Carmo Pimentel Batitucci

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  1. Daniela Camporez
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  2. Luciano Belcavello
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Correspondence to Jucimara Ferreira Figueiredo Almeida.

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Camporez, D., Belcavello, L., Almeida, J.F.F. et al. Positive association of a Sirt1 variant and parameters of oxidative stress on Alzheimer’s disease. Neurol Sci 42, 1843–1851 (2021). https://doi.org/10.1007/s10072-020-04704-y

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