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Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson’s disease

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dc.contributor.authorThomas, George E.C.
dc.contributor.authorZarkali, Angeliki
dc.contributor.authorRyten, Mina
dc.contributor.authorShmueli, Karin
dc.contributor.authorGil Martínez, Ana Luisa
dc.contributor.authorLeyland, Louis-Ann
dc.contributor.authorMcColgan, Peter
dc.contributor.authorAcosta-Cabronero, Julio
dc.contributor.authorLees, Andrew J.
dc.contributor.authorWeil, Rimona S.
dc.contributor.departmentIngeniería de la Información y las Comunicaciones
dc.date.accessioned2026-02-24T13:39:44Z
dc.date.available2026-02-24T13:39:44Z
dc.date.copyright© The Author(s) (2021
dc.date.created2021
dc.date.issued2021-03-11
dc.description.abstractThe 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.
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dc.identifier.citationGeorge E C Thomas, Angeliki Zarkali, Mina Ryten, Karin Shmueli, Ana Luisa Gil-Martinez, Louise-Ann Leyland, Peter McColgan, Julio Acosta-Cabronero, Andrew J Lees, Rimona S Weil, Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson’s disease, Brain, Volume 144, Issue 6, June 2021, Pages 1787–1798, https://doi.org/10.1093/brain/awab084
dc.identifier.doihttps://doi.org/10.1093/brain/awab084
dc.identifier.eissn1460-2156
dc.identifier.issn0006-8950
dc.identifier.urihttp://hdl.handle.net/10201/212342
dc.languageeng
dc.publisherOxford Univeristy Press
dc.relationMedical Research Council (MR/N013867/1; MR/N008324/1); Alzheimer’s Research UK (2018B-001); European Research Council (770939); Fundación Séneca (21230/PD/19); Wellcome Trust (205167/Z/16/Z); National Institute for Health Research; Parkinson’s UK; Cure Parkinson’s Trust; UCLH Biomedical Research Centre (BRC302/NS/RW/101410).
dc.relation.publisherversionhttps://academic.oup.com/brain/article/144/6/1787/6168127
dc.rightsAttribution 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectIron
dc.subjectQuantitative susceptibility mapping
dc.subjectGenetics
dc.subjectTranscriptomics
dc.subjectParkinson's disease
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleRegional brain iron and gene expression provide insights into neurodegeneration in Parkinson’s disease
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublicationes
relation.isAuthorOfPublication848746a7-05ac-4d08-82cb-e6a80680c24f
relation.isAuthorOfPublication.latestForDiscovery848746a7-05ac-4d08-82cb-e6a80680c24f
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