Altered Gene Co-expression Landscapes in the Parkinson's Disease Brain at Single-Nucleus Resolution

Protein biomarkers such as -synuclein, amyloid-beta 42, and neurofilament light chain (NF-L) are crucial for the diagnosis and study of Parkinson's Disease (PD). However, the behavior of the genes encoding these markers, including SNCA, APP, and NEFL, at the single-nucleus level within the diseased brain remains poorly understood. Leveraging recent advances in single-cell transcriptomics, this study analyzes a publicly available dataset from the prefrontal cortex to compare these diagnostic marker genes in PD patients and healthy controls (HC). Our analysis reveals two key findings: a significant downregulation of NEFL expression in excitatory neurons and a profound, cell-type-specific remodeling of the co-expression network between all three genes, particularly in glial cells. These results provide a cellular-level mechanism for established biomarkers and demonstrate that the pathology of PD involves a complex rewiring of gene networks, offering new insights for future diagnostic strategies.