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Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains

ABSTRACT: Parkinson’s disease (PD) is a common neurodegenerative disorder where recent evidence suggests may be mediated by inflammatory processes. The molecular architecture of the disease remains to be elucidated. We performed single-nucleus transcriptomics and unbiased proteomics using postmortem tissue obtained from the prefrontal cortex of 12 individuals with late-stage PD and age-matched controls. We analyzed ~80,000 nuclei and identified eight major cell types, including brain-resident T cells, each with distinct transcriptional changes in line with the known genetics of PD. By analyzing Lewy body pathology in the same tissue, we determined that α-synuclein pathology is inversely correlated to chaperone expression in excitatory neurons. Examining cell-cell interactions, we found a selective abatement of neuron-astrocyte interactions and enhanced neuroinflammation. Proteomic analyses of the same brains identified synaptic proteins that were preferentially negatively impacted in PD. Strikingly, comparing this dataset to a similar published analysis for Alzheimer’s disease (AD), we found no common, differentially expressed genes in neurons, but identified many in glial cells, suggesting that disease etiology in PD and AD are distinct. These data are presented as a resource for interrogating the molecular and cellular basis of PD and other neurodegenerative diseases.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Prefrontal Cortex

DISEASE(S): Parkinson's Disease

SUBMITTER: TuKiet Lam

LAB HEAD: TuKiet Lam

PROVIDER: PXD030142 | Pride | 2024-09-11

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	LF20-007_Chandra-Zhang_CTR-vs-PD_rnk10.mgf	Mgf
	LF20-007_Chandra-Zhang_CTR-vs-PD_rnk10_F521966.xml	Xml
	OTF20-2450_Chandra_hSDG07_CTR_F.raw	Raw
	OTF20-2455_Chandra_hSDG10_CTR_M.raw	Raw
	OTF20-2460_Chandra_hSDG151_PD_F.raw	Raw

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Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains

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