Fig. 7
Schema of hemispheric asymmetry in the epigenome of the healthy and PD brain. Neurons of the human prefrontal cortex exhibit prominent hemispheric asymmetry in DNA methylation. DNA methylation levels are higher in neurons of the left hemisphere, a difference driven largely by the accumulation of CpH methylation. Compared to neurons in the control brain, neurons in the PD brain possess considerably greater hemispheric asymmetry, again primarily driven by differential CpH methylation. Hemispheric asymmetry in PD involves DNA methylation abnormalities that are more prominent on the hemisphere matched to the side of symptom dominance. Aberrant hemispheric asymmetry and symptom lateralization in PD is related to disruption of genes affecting neurodevelopment, immune activation, and synaptic transmission. In aging, neuronal epigenomes exhibit a decrease in hemispheric asymmetry. The convergence of neuronal epigenomes in PD with aging may contribute to the bilateralization of PD symptoms over time, though hemispheric asymmetry in DNA methylation persists even at advanced ages. Epigenetic asymmetry between hemispheres is also linked to disease progression: PD patients with long (> 15 years) disease courses have greater asymmetry than patients with short (≤ 15 years) disease courses. Shading of brain hemispheres represents asymmetry in DNA methylation between paired hemispheres (shading represents DNA methylation status)