Single Cell Atlas of Human Putamen Reveals Disease Specific Changes in Synucleinopathies: Parkinson's Disease and Multiple System Atrophy [article]

Rahul Pande, Yinyin Huang, Erin Teeple, Pooja Joshi, Amilcar Flores-Morales, Martine Latta- Mahieu, S. Pablo Sardi, Angel Cedazo-Minguez, Katherine W. Klinger, Stephen L. Madden, Deepak Rajpal, Dinesh Kumar
2021 bioRxiv   pre-print
Understanding disease biology at a cellular level from disease specific tissues is imperative for effective drug development for complex neurodegenerative diseases. We profiled 87,086 nuclei from putamen tissue of healthy controls, Parkinson's Disease (PD), and Multiple System Atrophy (MSA) subjects to construct a comprehensive single cell atlas. Although both PD and MSA are manifestations of alpha-synuclein protein aggregation, we observed that both the diseases have distinct cell-type
more » ... changes. We see a possible expansion and activation of microglia and astrocytes in PD compared to MSA and controls. Contrary to PD microglia, we found absence of upregulated unfolded protein response in MSA microglia compared to controls. Differentially expressed genes in major cell types are enriched for genes associated with PD-GWAS loci. We found altered expression of major neurodegeneration associated genes, SNCA, MAPT, LRRK2, and APP, at cell-type resolution. We also identified disease associated gene modules using a network biology approach. Overall, this study creates an interactive atlas from synucleinopathies and provides major cell-type specific disease insights.
doi:10.1101/2021.05.06.442950 fatcat:2xxhyvajrbdg5lxds5wjcsujwa