Cingulate networks associated with gray matter loss in Parkinson's disease show high expression of cholinergic genes in the healthy brain

Structural covariance networks are able to identify functionally organized brain regions by gray matter volume covariance across a population. We examined the transcriptomic signature of such anatomical networks in the healthy brain using postmortem microarray data from the Allen Human Brain Atlas. A previous study revealed that a posterior cingulate network and anterior cingulate network showed decreased gray matter in brains of Parkinson's disease patients. Therefore, we examined these two anatomical networks to understand the underlying molecular processes that may be involved in Parkinson's disease. Whole brain transcriptomics from the healthy brain revealed upregulation of genes associated with serotonin, GPCR, GABA, glutamate, and RAS-signaling pathways. Our results also suggest involvement of the cholinergic circuit, in which genes NPPA, SOSTDC1, and TYRP1 may play a functional role. Finally, both networks were enriched for genes associated with neuropsychiatric disorders that overlap with Parkinson's 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 Parkinson's disease.

Automated summary

Structural covariance networks in healthy brains reveal upregulation of genes associated with serotonin, GPCR, GABA, glutamate, and RAS-signaling pathways. The involvement of the cholinergic circuit, as well as genes associated with neuropsychiatric disorders, may play a role in Parkinson's disease pathology. The disruption of healthy functions in cingulate networks could contribute to Parkinson's disease clinical events.