https://orcid.org/0000-0002-3674-7101
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Abstract
Aim: Noninvasive biomarkers such as methylated ccfDNA from plasma could help to support the diagnosis of Alzheimer’s disease (AD). Methods: A targeted sequencing protocol was developed to identify candidate biomarkers of AD in methylated ccfDNA extracted from plasma. Results: The authors identified differentially methylated CpGs, regions of which were the same as those identified in previous AD studies. Specifically, a differentially methylated CpG of the LHX2 gene previously identified in a plasma study of AD was replicated in the study. The MBP and DUSP22 regions have been identified in other brain studies of AD and in the authors’ study. Conclusion: Although these biomarkers must be validated in other cohorts, methylated ccfDNA could be a relevant noninvasive biomarker in AD.
Plain language summary
Currently, the diagnosis of Alzheimer’s disease (AD) is based on symptoms and medical imaging, and definitive clinical diagnosis is only possible postmortem. The identification of noninvasive biomarkers such as methylated ccfDNA is crucial for the diagnosis, prognosis and monitoring of AD. However, the analysis of ccfDNA from plasma is a challenge because it is highly fragmented and present in low amounts and originates from various tissues. The authors developed a targeted sequencing protocol using genes previously reported in AD literature (brain, blood and plasma) to identify potential noninvasive biomarkers in plasma. The authors identified positions identical to those in the literature as well as potential novel sites located in the promoter, exon and intron regions of these genes. Although these results must be validated in a large cohort, methylated ccfDNA could be a useful noninvasive biomarker for AD.
Graphical abstract
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2021-0491
Author Contributions
J Guemri, F Mauger and J-F Deleuze conceived the study. F Mauger and J-F Deleuze supervised the study. J Guemri and C Horgues performed the experiments. J Guemri, S Brohard and E Bonnet performed the data treatment. J Guemri, M Pierre-Jean and N Oussada performed the statistical analysis. J Guemri and F Mauger drafted the manuscript. All authors reviewed and approved the manuscript.
Acknowledgments
The authors would like to thank S McGinn for English language editing of the manuscript and the production platforms in the human genomics laboratory at the Centre National de Recherche en Génomique Humaine for loading the sequencing libraries on the flow cell.
Financial & competing interests disclosure
The study was funded by the institutional budget of the Centre National de Recherche en Génomique Humaine, Le Laboratoire d’Excellence en Genomique Medicale (ANR-10-LABX-0013), France Génomique (ANR-10-INBS-0009) and the European Union’s Horizon 2020 research and innovation programme (European Advanced infraStructure for Innovative Genomics) under grant agreement number 824110. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
BioIVT obtained informed consent for all subjects under institutional review board-approved protocols 5035 and 1108. The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.