Peripheral Blood BRCA1 Methylation Positively Correlates with Major Alzheimer's Disease Risk Factors.
Alzheimer’s disease
BRCA1
methylome
peripheral blood
Journal
The journal of prevention of Alzheimer's disease
ISSN: 2426-0266
Titre abrégé: J Prev Alzheimers Dis
Pays: Switzerland
ID NLM: 101638820
Informations de publication
Date de publication:
2021
2021
Historique:
entrez:
29
9
2021
pubmed:
30
9
2021
medline:
3
11
2021
Statut:
ppublish
Résumé
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. To analyze the methylation level of the BRCA1 promoter in peripheral blood from AD patients and normal controls. 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. Methylation level of the BRCA1 promoter was analyzed by pyrosequencing. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 34585223
doi: 10.14283/jpad.2021.31
doi:
Substances chimiques
Amyloid
0
BRCA1 Protein
0
BRCA1 protein, human
0
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
477-482Déclaration de conflit d'intérêts
None