Genetic and neurochemical profiles underlying cortical morphometric vulnerability to Parkinson's disease

Increasing evidence has documented cortical involvement at all stages of PD. The local vulnerabilities within certain brain regions in PD have been previously demonstrated, whereas its underlying genetic and neurochemical factors remain unclear. This study aims to investigate the spatial spectrum of cortical atrophy in Parkinson's disease (PD) and link these variances in gray matter properties and curvature respectively to putative molecular pathways and neurotransmitter factors.

We recruited 141 clinically diagnosed PD patients and 70 healthy controls. Cortical morphological abnormalities of PD were obtained by intergroup comparisons in gray matter properties metrics and curvature measurements. Then we performed gene-category enrichment and spatial correlation analyses to evaluate the specific correspondence between cortical alteration in PD and genetic expression from the Allen Human Brain Atlas and normative neurotransmitter atlases from Neuromaps.

We found decreased gray matter properties in temporal, somatomotor, cingulate and occipital cortices, decreased curvature measures in occipital, temporal and orbitofrontal cortices, and increased curvature measures in somatomotor, prefrontal and posterior parietal cortices for PD patients. The related genes were enriched for the glucose metabolism, mitochondrial function, and post-translational histone modifications processes. In addition, the serotonin and norepinephrine transporter devoted more to gray matter properties alterations while the dopamine, gamma-aminobutyric acid receptors, and norepinephrine transporter were strong contributors of curvature abnormalities in PD.

Collectively, the present study offered interpretation of cortical morphological alterations and the cortical pathogenic theory in PD from genetic and neurochemical perspectives, which inspire further research on new pharmacotherapeutic approaches.