Peripheral Blood BRCA1 Methylation Positively Correlates with Major Alzheimer’s Disease Risk Factors - 21/11/24
, K. Sato 1, T. Ikeuchi 2, T. Toda 1, T. Iwatsubo 3, A. Iwata 4Japanese Alzheimer’s Disease Neuroimaging Initiative
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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 celltype 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.
Le texte complet de cet article est disponible en PDF.Key words : Alzheimer’s disease, methylome, BRCA1, peripheral blood
Plan
| The full list of members of the Japanese Alzheimer’s Disease Neuroimaging Initiative is provided in the supplementary file, «J-ADNI co-investigators». |
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| How to cite this article: T. Mano, K. Sato, T. Ikeuchi, et al. Peripheral Blood BRCA1 Methylation Positively Correlates with Major Alzheimer’s Disease Risk Factors. J Prev Alz Dis 2021;jpad.2021.31 |
Vol 8 - N° 4
P. 477-482 - avril 2021 Retour au numéro
Article précédent
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