Unravelling cell type specific response to Parkinson’s Disease at single cell resolution

Araks Martirosyan, Francisco Pestana, Katja Hebestreit, Hayk Gasparyan, Razmik Aleksanyan, Suresh Poovathingal, Catherine Marneffe, Dietmar R. Thal, Andrew Kottick, Victor Hanson-Smith, Sebastian Guelfi, Emmanouil Metzakopian, T. Grant Belgard


Parkinson’s Disease (PD) is the second most common neurodegenerative disorder and is generally characterized by impaired motor functions. It currently affects 6.3 million people aged 60 years and more, worldwide. The pathological hallmarks of PD are Lewy bodies (abnormal aggregation of α-synuclein inside cells), which are observed primarily in the substantia nigra (SN) region of the midbrain. It is yet not known how different cell types in SN respond during PD and what are the molecular mechanisms underlying neurodegeneration. To address this question, we generated a large-scale single cell transcriptomics dataset from human post-mortem SN tissue of 29 donors including 15 sporadic cases and 14 controls. We obtained data for a total of ∼80K nuclei, representing major cell types of the brain (including neurons, astrocytes, microglia and oligodendrocytes). Pathway and differential gene expression analysis revealed multicellular character of PD pathology involving major cellular response from neuronal and glial cells.

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