Neurogenetic traits outline vulnerability to cortical disruption in Parkinson's disease

Abstract

The genetic traits that underlie vulnerability to neuronal damage across specific brain circuits in Parkinson's disease (PD) remain to be elucidated. In this study, we characterized the brain topological intersection between propagating connectivity networks in controls and PD participants and gene expression patterns across the human cortex - such as the SNCA gene. We observed that brain connectivity originated from PD-related pathology epicenters in the brainstem recapitulated the anatomical distribution of alpha-synuclein histopathology in postmortem data. We also discovered that the gene set most related to cortical propagation patterns of PD-related pathology was primarily involved in microtubule cellular components. Thus, this study sheds light on new avenues for enhancing detection of PD neuronal vulnerability via an evaluation of in vivo connectivity trajectories across the human brain and successful integration of neuroimaging-genetic strategies. ; Acknowledgment: The authors thank the patients and their families for the time and effort they dedicated to the research. Funding This research was supported by grants from the National Institutes of Health (NIH; R01AG061811, and R01AG061445 to J.S.), the Ministry of Education, Science, and Technological Development of the Republic of Serbia (grant number 175090), the Italian Ministry of Health (grant number RF-2018-12366746), the Carlos III Institute of Health (PI11/02109) Spain, the Basque Government through the BERC 2018-2021 program and the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation SEV-2015-0490.