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

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Vis graf over relationer

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.

OriginalsprogEngelsk
Artikelnummer140
TidsskriftInternational Journal of Molecular Sciences
Vol/bind22
Udgave nummer1
Sider (fra-til)1-17
Antal sider17
ISSN1661-6596
DOI
StatusUdgivet - 1 jan. 2021

Bibliografisk note

Funding Information:
Acknowledgments: The authors thank Edinburgh Brain Bank, which is funded by the United Kingdom Medical Research Council, for providing healthy brain tissues used as controls.

ID: 62294302