Cited by 13Prion Diseases and Protein MisfoldingNeuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatments

Regional Differences in Neuroinflammation-Associated Gene Expression in the Brain of Sporadic Creutzfeldt–Jakob Disease Patients

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Areškevičiūtė, Aušrinė, Litman, Thomas, Broholm, Helle, Melchior, Linea C., Nielsen, Pia R., Green, Alison, Eriksen, Jens O., Smith, Colin +1 more·2020·International Journal of Molecular Sciences

Abstract

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.

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  • Bulk expression analysis in two brain regions in sCJD displays regionally distinct inflammatory profiles.

    “However, bulk expression analysis in two brain regions in sCJD displayed regionally distinct inflammatory profiles [114].”

    From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [114]

  • Regional differences in inflammation-associated expression changes are beginning to be investigated and described in the frontal cortex and cerebellum of patients with sCJD.

    “As already determined in the murine models in more detail (see above), the regional differences in inflammation-associated expression changes are also beginning to be investigated and described in the frontal cortex and cerebellum of patients with sCJD [114].”

    From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [114]

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Authors
Areškevičiūtė, A., Litman, T., Broholm, H., Melchior, L. C., Nielsen, P. R., Green, A., Eriksen, J. O., Smith, C., & Lund, E. L.
Affiliations
  • Copenhagen University Hospital (DK)
  • University of Copenhagen (DK)
  • Zealand University Hospital (DK)
  • University of Edinburgh (GB)
Corresponding author
Areškevičiūtė, Aušrinė
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-12-25
Volume
22
Issue
1
Pages
140
ISSN
1422-0067 (ISSN-L)
OpenAlex
W3117790131
Cited by
13
References
49
Citations by year
2026: 3 · 2025: 1 · 2023: 4 · 2022: 4 · 2021: 1
FWCI
0.73
Type
journal article
Language
en
Open access
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
Funders
Medical Research Council (MR/J016071/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
sporadic Creutzfeldt-Jakob disease, neuroinflammation, gene expression profiling, regional brain differences, frontal cortex, cerebellum, prion disease, neurodegeneration, differentially expressed genes, canonical pathways, upstream regulators, molecular subtypes
MeSH terms
Aged, Brain, Disease Susceptibility, Female, Humans, Creutzfeldt-Jakob Syndrome, Male, Middle Aged, Biomarkers, Gene Expression, Computational Biology, Gene Expression Profiling, Transcriptome, Cellular Microenvironment

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