Journal of Molecular Neuroscience

, Volume 62, Issue 2, pp 215–221 | Cite as

Validating GWAS Variants from Microglial Genes Implicated in Alzheimer’s Disease

  • Lígia Ramos dos SantosEmail author
  • Lúcia Helena Sagrillo Pimassoni
  • Geralda Gillian Silva Sena
  • Daniela Camporez
  • Luciano Belcavello
  • Maíra Trancozo
  • Renato Lírio Morelato
  • Flavia Imbroisi Valle Errera
  • Maria Rita Passos Bueno
  • Flavia de Paula


Late-onset Alzheimer’s disease (LOAD) is a multifactorial neurodegenerative disorder that corresponds to most Alzheimer’s disease (AD) cases. Inflammation is frequently related to AD, whereas microglial cells are the major phagocytes in the brain and mediate the removal of Aβ peptides. Microglial cell dsyregulation might contribute to the formation of amyloid plaques, a hallmark of AD. Genome-wide association studies have reported genetic loci associated with the inflammatory pathway involved in AD. Among them, rs3865444 CD33, rs3764650 ABCA7, rs6656401 CR1, and rs610932 MS4A6A variants in microglial genes are associated with LOAD. These variants are proposed to participate in the clearance of Aβ peptides. However, their association with LOAD was not validated in all case-control studies. Thus, the present work aimed to assess the involvement of CD33 (rs3865444), ABCA7 (rs3764650), CR1 (rs6656401), and MS4A6A (rs610932) with LOAD in a sample from southeastern Brazil. The genotype frequencies were assessed in 79 AD patients and 145 healthy elders matched for sex and age. We found that rs3865444 CD33 acts as a protective factor against LOAD. These results support a role for the inflammatory pathway in LOAD.


Load Case-control study Microglial genes Polymorphisms 



We appreciate the support of the researchers from the Núcleo de Genética Humana e Molecular – NGHM, Brazil. We thank the Instituto de Biociência, Universidade de São Paulo and Núcleo de Biotecnologia, Universidade Federal do Espírito Santo, Brazil for technical support. This study was financially supported by the Universidade Federal do Espírito Santo – UFES; Fundo de Amparo e Pesquisa do Espírito Santo – FAPES; Departamento de Ciência e Tecnologia do Ministério da Saúde - Decit; Secretaria de Ciência, Tecnologia e Insumos Estratégicos do Ministério da Saúde - SCTIE/MS; Fundo de Apoio à Ciência e Tecnologia do Município de Vitória - FACITEC; Ministério da Ciência, Tecnologia e Inovação - MCTI; Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPQ; Ministério da Educação – MEC and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Lígia Ramos dos Santos
    • 1
    • 2
    Email author
  • Lúcia Helena Sagrillo Pimassoni
    • 3
  • Geralda Gillian Silva Sena
    • 1
    • 4
  • Daniela Camporez
    • 1
    • 2
  • Luciano Belcavello
    • 1
  • Maíra Trancozo
    • 1
    • 2
  • Renato Lírio Morelato
    • 3
    • 5
  • Flavia Imbroisi Valle Errera
    • 2
    • 3
  • Maria Rita Passos Bueno
    • 6
  • Flavia de Paula
    • 1
    • 2
  1. 1.Laboratório de Genética Humana e Molecular, Departamento de Ciências Biológicas, Centro de CiênciasHumanas e NaturaisUniversidade Federal do Espírito SantoVitóriaBrazil
  2. 2.Programa de Pós-Graduação em BiotecnologiaUniversidade Federal do Espírito SantoVitóriaBrazil
  3. 3.Escola Superior de Ciências da Santa Casa de Misericórdia de VitóriaVitóriaBrazil
  4. 4.Departamento de Educação Integrada em Saúde, Centro de Ciências da SaúdeUniversidade Federal do Espírito SantoVitóriaBrazil
  5. 5.Hospital da Santa Casa de Misericórdia de Vitória, Escola Superior de Ciências da Santa Casa de Misericórdia de VitóriaVitóriaBrazil
  6. 6.Universidade de São PauloSão PauloBrazil

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