Fig. 1

Overview of study workflow utilizing genome-wide methylation analysis of plasma-derived cfDNA to identify age-related and ALS-associated methylation signatures. Plasma samples were collected from 30 individuals, including healthy participants from various age groups, ALS patients, and age- and gender-matched control subjects. Methylome profiling of cfDNA was conducted using WGBS on bisulfite-treated cfDNA. Age-related and ALS-associated methylation signatures were identified through comprehensive bioinformatic analysis. Additionally, the correlation between ALS-related methylation profiles and gene dysregulation in CNS tissues derived from ALS patients was investigated at both the bulk and single-cell levels. A reference-based deconvolution analysis was performed to determine the tissue and cell-type origins of the cfDNA