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Single-nuclei paired multiomic analysis of young, aged, and Parkinson’s disease human midbrain reveals age-associated glial changes and their contribution to Parkinson’s disease

ABSTRACT: Age is the primary risk factor for Parkinson’s disease (PD), but how aging changes the expression and regulatory landscape of the brain remains unclear. Here, we present a single-nuclei multiomic study profiling shared gene expression and chromatin accessibility of young, aged and PD post-mortem midbrain samples. Combined multiomic analysis of midbrain nuclei along a pseudopathogenesis trajectory reveals all glial cell types are affected by age, but microglia and oligodendrocytes are further altered in PD. We present evidence for a novel age-associated oligodendrocyte subtype that appears during normal aging, characterized by elevated protein folding and chaperone-mediated autophagy pathways. Differential gene and protein-protein interaction analyses show that these functions are significantly compromised in PD. Peak-gene association from our paired data identifies differential cis-elements linked to regulation of differentially expressed genes between PD patients and neurologically healthy controls. Our study suggests a previously undescribed role for oligodendrocytes in aging and PD pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193688 | GEO | 2023/04/27

REPOSITORIES: GEO

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