Plasma neuron-derived cfDNA: Oxford Nanopore sequencing for neurodegenerative disease | LC 25

Biography

Jonathon Hill, Vice President of Science and Technology at Wasatch BioLabs (WBL) and an Associate Professor of Cell Biology and Physiology at Brigham Young University (BYU), develops innovative genomic and bioinformatic methods for gene expression analysis and variant detection. He is a Fulbright Scholar and a BYU Early-Career Teaching Award recipient, having received his MS in Molecular Biology from the University of Colorado Health Science Center, and a PhD in Genetics and Developmental Biology from Columbia University.

Abstract

Neurodegenerative diseases like Alzheimer’s (AD), Parkinson’s (PD), and amyotrophic lateral sclerosis (ALS) affect millions worldwide. Current detection methods often rely on clinical symptoms that appear after significant neuronal damage, limiting early intervention.

Cell-free DNA (cfDNA) in the blood offers a breakthrough opportunity for detecting early biomarkers of neurodegeneration, potentially before symptoms emerge. To explore neuron-specific cfDNA as a biomarker for neuronal death, we leverage Wasatch BioLabs-developed library preparation methods with nanopore sequencing to preserve native cfDNA methylation. This approach overcomes limitations of traditional bisulfite sequencing, enabling accurate methylation calls.

By identifying neuron-specific methylation signatures — cortical for AD, dopaminergic for PD, and motor neurons for ALS — we can precisely determine neuron-of-origin. A 400-sample pilot study revealed elevated neuron-derived cfDNA in patients with mild cognitive impairment (MCI), AD, PD, and ALS, demonstrating significant clinical potential.

An 800-sample longitudinal study for AD is currently underway in collaboration with Resonant, Brigham Young University (BYU), and the University of Kansas Alzheimer’s Disease.