Insights into Neurodegeneration in Parkinson's Disease from Single-Cell and Spatial Genomics

Parkinson's disease (PD) is pathologically defined by the death of dopaminergic (DA) neurons within the pars compacta of the substantia nigra. To date, the cause of this multifaceted disease remains largely unclear, which may contribute in part to a current lack of disease-modifying therapies. Recent advances in single-cell and spatial genomic profiling tools have provided powerful new ways to measure cellular state changes in brain diseases. Here, we describe how these tools have offered insight into these complex disorders and highlight a recently performed comprehensive study of DA neuron susceptibility in PD. The data generated by this recent work provide evidence for the role of specific pathways and common genetic variants resulting in the loss of a critical DA subtype in PD. We conclude by outlining a set of basic and translational opportunities that arise from those data and insights gathered from this work. © 2023 International Parkinson and Movement Disorder Society.