Fig. 1

Schematic of the study. The figure shows a schematic of the workflow for assessing brain-derived biomarkers in blood samples from bvFTD and PPD subjects. The study aimed to evaluate the clinical utility of brain-derived cell-free DNA (cfDNA) (and protein biomarkers e.g. NfL) in differentiating sporadic bvFTD subjects from PPD. (A) Blood samples were collected from PPD and bvFTD subjects (left) and (B) plasma cfDNA fragments were enriched from regions of the genome known to exhibit neuron- and glia-specific DNA methylation (5mC) patterns. (C) Targeted bisulfite sequencing was performed on 17 loci identified previously as displaying highly specific DNA methylation patterns in neurons and glia37. (D) The cfDNA methylation patterns obtained from sequencing were analyzed using the methylK lookup approach to match them with established neuron- and glia-specific 5mC profiles37. These patterns were then used to assign cfDNA fragments to their cell of origin.