Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson's disease.
IF: 15.255
Cited by: 30


The mechanisms 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 of 96 patients with Parkinson's disease and 35 control subjects 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. Applying gene ontological tools, we investigated the biological processes and cell types associated with this transcriptomic profile and identified the sets of genes with spatial expression profiles in control brains that 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. Furthermore, we demonstrated that the genes differentially expressed in Parkinson's disease are associated with the pattern of cortical expression identified in this study. Our findings provide mechanistic insights into regional selective vulnerabilities in Parkinson's disease, particularly the processes involving iron accumulation.


Parkinson’s disease
quantitative susceptibility mapping

MeSH terms

Aged, 80 and over
Image Interpretation, Computer-Assisted
Magnetic Resonance Imaging
Middle Aged
Nerve Degeneration
Oxidative Stress
Parkinson Disease


Thomas, George E C
Zarkali, Angeliki
Ryten, Mina
Shmueli, Karin
Gil-Martinez, Ana Luisa
Leyland, Louise-Ann
McColgan, Peter
Acosta-Cabronero, Julio
Lees, Andrew J
Weil, Rimona S

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