Cholinergic circuit genes in the healthy brain are differentially expressed in regions that exhibit gray matter loss in Parkinson's disease

Structural covariance networks are able to identify functionally organized brain regions by gray matter volume covariance. In Parkinson9s disease, the posterior cingulate network and anterior cingulate network showed decreased gray matter and therefore we examined the underlying molecular processes of these anatomical networks in the healthy brain. Whole brain transcriptomics from post-mortem samples from healthy adults, revealed upregulation of genes associated with serotonin, GPCR, GABA, glutamate, and RAS signaling pathways in these PD-related regions. Our results also suggest involvement of the cholinergic circuit, in which genes NPPA, SOSTDC1, and TYRP1 may play a protective role. Furthermore, both networks were associated with memory and neuropsychiatric disorders that overlap with Parkinson9s disease symptoms. The identified genes and pathways contribute to healthy functions of the posterior and anterior cingulate networks and disruptions to these functions may in turn contribute to the pathological and clinical events observed in Parkinson9s disease.