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@ARTICLE{Dehestani:271334,
      author       = {Dehestani, Mohammad and Kozareva, Velina and Blauwendraat,
                      Cornelis and Fraenkel, Ernest and Gasser, Thomas and Bansal,
                      Vikas},
      title        = {{T}ranscriptomic changes in oligodendrocytes and precursor
                      cells associate with clinical outcomes of {P}arkinson's
                      disease.},
      journal      = {Molecular brain},
      volume       = {17},
      number       = {1},
      issn         = {1756-6606},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DZNE-2024-01036},
      pages        = {56},
      year         = {2024},
      abstract     = {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.},
      keywords     = {Parkinson Disease: genetics / Parkinson Disease: pathology
                      / Humans / Oligodendroglia: metabolism / Oligodendroglia:
                      pathology / Transcriptome: genetics / Male / Female / Aged /
                      Oligodendrocyte Precursor Cells: metabolism / Cohort Studies
                      / Middle Aged / Oligodendrocyte precursor cells (Other) /
                      Oligodendrocytes (Other) / PD symptoms (Other) /
                      Parkinson’s disease (Other) / Polygenic risk scores
                      (Other) / snRNA-seq (Other)},
      cin          = {AG Bansal / AG Gasser},
      ddc          = {610},
      cid          = {I:(DE-2719)1210013 / I:(DE-2719)1210000},
      pnm          = {354 - Disease Prevention and Healthy Aging (POF4-354) / 353
                      - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-354 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39138468},
      pmc          = {pmc:PMC11323592},
      doi          = {10.1186/s13041-024-01128-z},
      url          = {https://pub.dzne.de/record/271334},
}