Circulating Cell-Free DNA Methylation Profiles Enable Disease-Specific Detection of Alzheimer's, Parkinson's, and ALS from Blood
Jenkins, T.; Pollard, C.; Saito, E.; Stirland, I.; Miller, R.; Keni, M.; Jenkins, A.; Hill, J. T.
Show abstract
Noninvasive biomarkers for neurodegenerative diseases are urgently needed for earlier detection, monitoring, and intervention. To address this, we developed a blood-based cfDNA methylation platform. A whole-genome nanopore methylation atlas of six primary human neural cell types--cortical, dopaminergic, and spinal motor neurons, astrocytes, Schwann cells, microglia--was used to train classifiers that assign cfDNA to its neuronal or glial origin. Classifiers were validated in silico and applied to 219 plasma samples from patients with Alzheimers disease (AD), Parkinsons disease (PD), amyotrophic lateral sclerosis (ALS), and controls. Cortical cfDNA was elevated in AD, dopaminergic cfDNA in PD, and spinal motor neuron cfDNA in ALS, with predictive modeling achieving AUCs >0.98. In mild cognitive impairment, cortical cfDNA elevations identified individuals who later progressed to AD, supporting predictive utility. A multivariate model integrating multiple neurons improved accuracy, suggesting cfDNA methylation profiling as a scalable framework for noninvasive neurodegeneration detection and monitoring.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Molecular Signatures of Resilience to Alzheimer's Disease in Neocortical Layer 4 Neurons 95%
- A meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex 94%
- DNA methylation signatures of Alzheimer's disease neuropathology in the cortex are primarily driven by variation in non-neuronal cell-types 94%