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@MISC{Dehestani:271085,
author = {Dehestani, Mohammad and Kozareva, V. and Blauwendraat,
Cornelis and Fränkel, E. and Gasser, Thomas and Bansal,
Vikas},
title = {{D}ataset: {T}ranscriptomic changes in oligodendrocytes and
precursor cells predicts clinical outcomes of {P}arkinson's
disease},
publisher = {Gene Expression Omnibus},
reportid = {DZNE-2024-00957},
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
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 three separate datasets that
were previously published by different laboratories. In the
first dataset from the anterior cingulate cortex, we
identified a correlation between ODCs and BDI-II. In the
second dataset obtained from the substantia nigra (SN), OPCs
displayed notable predictive ability for UPDRS-III. In the
third dataset from the SN region, a distinct subtype of
OPCs, labeled $OPC_ADM,$ exhibited predictive ability for
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.},
cin = {AG Bansal / AG Gasser},
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)32},
url = {https://pub.dzne.de/record/271085},
}