TY  - JOUR
AU  - Dehestani, Mohammad
AU  - Kozareva, Velina
AU  - Blauwendraat, Cornelis
AU  - Fraenkel, Ernest
AU  - Gasser, Thomas
AU  - Bansal, Vikas
TI  - Transcriptomic changes in oligodendrocytes and precursor cells associate with clinical outcomes of Parkinson's disease.
JO  - Molecular brain
VL  - 17
IS  - 1
SN  - 1756-6606
CY  - London
PB  - BioMed Central
M1  - DZNE-2024-01036
SP  - 56
PY  - 2024
AB  - Several 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.
KW  - Parkinson Disease: genetics
KW  - Parkinson Disease: pathology
KW  - Humans
KW  - Oligodendroglia: metabolism
KW  - Oligodendroglia: pathology
KW  - Transcriptome: genetics
KW  - Male
KW  - Female
KW  - Aged
KW  - Oligodendrocyte Precursor Cells: metabolism
KW  - Cohort Studies
KW  - Middle Aged
KW  - Oligodendrocyte precursor cells (Other)
KW  - Oligodendrocytes (Other)
KW  - PD symptoms (Other)
KW  - Parkinson’s disease (Other)
KW  - Polygenic risk scores (Other)
KW  - snRNA-seq (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39138468
C2  - pmc:PMC11323592
DO  - DOI:10.1186/s13041-024-01128-z
UR  - https://pub.dzne.de/record/271334
ER  -