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000271334 1001_ $$0P:(DE-2719)9002232$$aDehestani, Mohammad$$b0$$eFirst author$$udzne
000271334 245__ $$aTranscriptomic changes in oligodendrocytes and precursor cells associate with clinical outcomes of Parkinson's disease.
000271334 260__ $$aLondon$$bBioMed Central$$c2024
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000271334 520__ $$aSeveral prior studies have proposed the involvement of various brain regions and cell types in Parkinson's disease (PD) pathology. Here, we performed snRNA-seq on the prefrontal cortex and anterior cingulate regions from a small cohort of post-mortem control and PD brain tissue. We found a significant association of oligodendrocytes (ODCs) and oligodendrocyte precursor cells (OPCs) with PD-linked risk loci and report several dysregulated genes and pathways, including regulation of tau-protein kinase activity, regulation of inclusion body assembly and protein processing involved in protein targeting to mitochondria. In an independent PD cohort with clinical measures (681 cases and 549 controls), polygenic risk scores derived from the dysregulated genes significantly predicted Montreal Cognitive Assessment (MoCA)-, and Beck Depression Inventory-II (BDI-II)-scores but not motor impairment (UPDRS-III). We extended our analysis of clinical outcome prediction by incorporating differentially expressed genes from three separate datasets that were previously published by different laboratories. In the first dataset from the anterior cingulate cortex, we identified an association between ODCs and BDI-II. In the second dataset obtained from the substantia nigra (SN), OPCs displayed an association with UPDRS-III. In the third dataset from the SN region, a distinct subtype of OPCs, labeled OPC_ADM, exhibited an association with UPDRS-III. Intriguingly, the OPC_ADM cluster also demonstrated a significant increase in PD samples. These results suggest that by expanding our focus to glial cells, we can uncover region-specific molecular pathways associated with PD symptoms.
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000271334 650_7 $$2Other$$aOligodendrocyte precursor cells
000271334 650_7 $$2Other$$aOligodendrocytes
000271334 650_7 $$2Other$$aPD symptoms
000271334 650_7 $$2Other$$aParkinson’s disease
000271334 650_7 $$2Other$$aPolygenic risk scores
000271334 650_7 $$2Other$$asnRNA-seq
000271334 650_2 $$2MeSH$$aParkinson Disease: genetics
000271334 650_2 $$2MeSH$$aParkinson Disease: pathology
000271334 650_2 $$2MeSH$$aHumans
000271334 650_2 $$2MeSH$$aOligodendroglia: metabolism
000271334 650_2 $$2MeSH$$aOligodendroglia: pathology
000271334 650_2 $$2MeSH$$aTranscriptome: genetics
000271334 650_2 $$2MeSH$$aMale
000271334 650_2 $$2MeSH$$aFemale
000271334 650_2 $$2MeSH$$aAged
000271334 650_2 $$2MeSH$$aOligodendrocyte Precursor Cells: metabolism
000271334 650_2 $$2MeSH$$aCohort Studies
000271334 650_2 $$2MeSH$$aMiddle Aged
000271334 7001_ $$aKozareva, Velina$$b1
000271334 7001_ $$0P:(DE-2719)2810837$$aBlauwendraat, Cornelis$$b2
000271334 7001_ $$aFraenkel, Ernest$$b3
000271334 7001_ $$0P:(DE-2719)2320009$$aGasser, Thomas$$b4$$udzne
000271334 7001_ $$0P:(DE-2719)2812055$$aBansal, Vikas$$b5$$eLast author
000271334 773__ $$0PERI:(DE-600)2436057-0$$a10.1186/s13041-024-01128-z$$gVol. 17, no. 1, p. 56$$n1$$p56$$tMolecular brain$$v17$$x1756-6606$$y2024
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