Peripheral Blood BRCA1 Methylation Positively Correlates with Major Alzheimer's Disease Risk Factors.

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  • Author(s): Mano T;Mano T; Sato K; Ikeuchi T; Toda T; Iwatsubo T; Iwata A
  • Source:
    The journal of prevention of Alzheimer's disease [J Prev Alzheimers Dis] 2021; Vol. 8 (4), pp. 477-482.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Springer International Publishing Country of Publication: Switzerland NLM ID: 101638820 Publication Model: Print Cited Medium: Internet ISSN: 2426-0266 (Electronic) Linking ISSN: 22745807 NLM ISO Abbreviation: J Prev Alzheimers Dis Subsets: MEDLINE
    • Publication Information:
      Publication: <2018>: [Cham, Switzerland] : Springer International Publishing
      Original Publication: Auzeville-Tolosane : SERDI éd., [2014]-
    • Subject Terms:
    • Abstract:
      Background: Recent biomarker studies demonstrated that the central nervous system (CNS) environment can be observed from peripherally-derived samples. In a previous study, we demonstrated significant hypomethylation of the BRCA1 promoter region in neuronal cells from post-mortem brains of Alzheimer's disease patients through neuron-specific methylome analysis. Thus, we investigate the methylation changes in the BRCA1 promoter region in the blood samples.
      Objectives: To analyze the methylation level of the BRCA1 promoter in peripheral blood from AD patients and normal controls.
      Design, Setting, Participants: Genomic DNA samples from peripheral blood were obtained from the J-ADNI repository, and their biomarker data were obtained J-ADNI from the National Bioscience Database Center. Genomic DNA samples from an independent cohort for validation was obtained from Niigata University Hospital (Niigata, Japan). Amyloid positivity was defied by visual inspection of amyloid PET or a CSF Aβ42 value ≤ 333 pg/mL at the baseline.
      Measurements: Methylation level of the BRCA1 promoter was analyzed by pyrosequencing.
      Results: Compared to normal controls, methylation of the BRCA1 promoter in AD patients was not significantly changed; however, in AD patients, it showed a positive correlation with AD risk factors.
      Conclusions: Our data confirmed the importance of cell-type specific methylome analysis and also suggested that environmental changes in the CNS can be detected by observing the peripheral blood, implying that the peripheral BRCA1 methylation level can be a surrogate for AD.
      Competing Interests: None
    • Contributed Indexing:
      Keywords: Alzheimer’s disease; BRCA1; methylome; peripheral blood
    • Accession Number:
      0 (Amyloid)
      0 (BRCA1 Protein)
      0 (BRCA1 protein, human)
      0 (Biomarkers)
    • Publication Date:
      Date Created: 20210929 Date Completed: 20211101 Latest Revision: 20220123
    • Publication Date:
      20240829
    • Accession Number:
      10.14283/jpad.2021.31
    • Accession Number:
      34585223