| Autor: |
Lucia A. A. Giannini, Ruben G. Boers, Emma L. van derEnde, Jackie M. Poos, Lize C. Jiskoot, Joachim B. Boers, Wilfred F. J. vanIJcken, Elise G. Dopper, Yolande A. L. Pijnenburg, Harro Seelaar, Lieke H. Meeter, Jeroen G. J. vanRooij, Wiep Scheper, Joost Gribnau, John C. vanSwieten |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Annals of Clinical and Translational Neurology, Vol 11, Iss 3, Pp 744-756 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2328-9503 |
| DOI: |
10.1002/acn3.51997 |
| Popis: |
Abstract Objective Methylation of plasma cell‐free DNA (cfDNA) has potential as a marker of brain damage in neurodegenerative diseases such as frontotemporal dementia (FTD). Here, we study methylation of cfDNA in presymptomatic and symptomatic carriers of genetic FTD pathogenic variants, next to healthy controls. Methods cfDNA was isolated from cross‐sectional plasma of 10 presymptomatic carriers (4 C9orf72, 4 GRN, and 2 MAPT), 10 symptomatic carriers (4 C9orf72, 4 GRN, and 2 MAPT), and 9 healthy controls. Genome‐wide methylation of cfDNA was determined using a high‐resolution sequencing technique (MeD‐seq). Cumulative scores based on the identified differentially methylated regions (DMRs) were estimated for presymptomatic carriers (vs. controls and symptomatic carriers), and reevaluated in a validation cohort (8 presymptomatic: 3 C9orf72, 3 GRN, and 2 MAPT; 26 symptomatic: 7 C9orf72, 6 GRN, 12 MAPT, and 1 TARDBP; 13 noncarriers from genetic FTD families). Results Presymptomatic carriers showed a distinctive methylation profile compared to healthy controls and symptomatic carriers. Cumulative DMR scores in presymptomatic carriers enabled to significantly differentiate presymptomatic carriers from healthy controls (p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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