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Rigshospitalet - a part of Copenhagen University Hospital
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Regional Differences in Neuroinflammation-Associated Gene Expression in the Brain of Sporadic Creutzfeldt-Jakob Disease Patients

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Neuroinflammation is an essential part of neurodegeneration. Yet, the current understanding of neuroinflammation-associated molecular events in distinct brain regions of prion disease patients is insufficient to lay the ground for effective treatment strategies targeting this complex neuropathological process. To address this problem, we analyzed the expression of 800 neuroinflammation-associated genes to create a profile of biological processes taking place in the frontal cortex and cerebellum of patients who suffered from sporadic Creutzfeldt-Jakob disease. The analysis was performed using NanoString nCounter technology with human neuroinflammation panel+. The observed gene expression patterns were regionally and sub-regionally distinct, suggesting a variable neuroinflammatory response. Interestingly, the observed differences could not be explained by the molecular subtypes of sporadic Creutzfeldt-Jakob disease. Furthermore, analyses of canonical pathways and upstream regulators based on differentially expressed genes indicated an overlap between biological processes taking place in different brain regions. This suggests that even smaller-scale spatial data reflecting subtle changes in brain cells' functional heterogeneity and their immediate pathologic microenvironments are needed to explain the observed differential gene expression in a greater detail.

Original languageEnglish
Article number140
JournalInternational Journal of Molecular Sciences
Volume22
Issue number1
Pages (from-to)1-17
Number of pages17
ISSN1661-6596
DOIs
Publication statusPublished - 1 Jan 2021

Bibliographical note

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

    Research areas

  • Biomarkers, Brain microenvironment, Creutzfeldt–Jakob disease, Gene expression analysis, Immune re-sponse, Microglia, Neuroinflammation, Prion disease, Regional pathogenesis

ID: 62294302