AI Article Synopsis

  • Parkinson's disease (PD) is linked to inflammation, and researchers studied brain cells in late-stage PD using advanced techniques to understand vulnerabilities.
  • They analyzed brain samples from six PD patients and six healthy controls, identifying distinct changes in eight cell types, including increased T cells in PD and marked alterations in excitatory neurons.
  • Comparisons with Alzheimer's disease revealed that while neuron changes were different, both diseases shared some changes in glial cells, indicating unique underlying mechanisms for neuronal vulnerability in PD versus AD.

Article Abstract

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, and recent evidence suggests that pathogenesis may be in part mediated by inflammatory processes, the molecular and cellular architectures of which are largely unknown. To identify and characterize selectively vulnerable brain cell populations in PD, we performed single-nucleus transcriptomics and unbiased proteomics to profile the prefrontal cortex from postmortem human brains of six individuals with late-stage PD and six age-matched controls. Analysis of nearly 80,000 nuclei led to the identification of eight major brain cell types, including elevated brain-resident T cells in PD, each with distinct transcriptional changes in agreement with the known genetics of PD. By analyzing Lewy body pathology in the same postmortem brain tissues, we found that α-synuclein pathology was inversely correlated with 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 in the prefrontal cortex that were preferentially down-regulated in PD. By comparing this single-cell PD dataset with a published analysis of similar brain regions in Alzheimer's disease (AD), we found no common differentially expressed genes in neurons but identified many shared differentially expressed genes in glial cells, suggesting that the disease etiologies, especially in the context of neuronal vulnerability, in PD and AD are likely distinct.

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Source
http://dx.doi.org/10.1126/scitranslmed.abo1997DOI Listing

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