Abstract
The mechanisms which are responsible for the selective vulnerability of specific neuronal populations in Parkinson’s disease are poorly understood. Oxidative stress secondary to brain iron accumulation is one postulated mechanism. We measured iron deposition in 180 cortical regions in 96 patients with Parkinson’s disease and 35 controls using quantitative susceptibility mapping. We estimated the expression of 15 745 genes in the same regions using transcriptomic data from the Allen Human Brain Atlas. Using partial least squares regression, we then identified the profile of gene transcription in the healthy brain that underlies increased cortical iron in patients with Parkinson’s disease relative to controls. With gene ontological tools, we investigated the biological processes and cell types associated with this transcriptomic profile. We identified the sets of genes whose spatial expression profiles in control brains correlated significantly with the spatial pattern of cortical iron deposition in Parkinson’s disease. Gene ontological analyses revealed that these genes were enriched for biological processes relating to heavy metal detoxification, synaptic function and nervous system development and were predominantly expressed in astrocytes and glutamatergic neurons. We also show that genes found to be differentially expressed in Parkinson’s disease play a role in explaining the pattern of cortical expression we identified. Our findings provide mechanistic insights into regional selective vulnerabilities in Parkinson’s disease, particularly into processes involving iron accumulation.
Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson’s disease
