Multi-Omics Data Modeling of Neurovascular Uncoupling Underlying Visual Hallucinations in Parkinson's Disease

摘要

Objective:Parkinson's disease with visual hallucinations(PDVH) is a common non-motor psychiatric symptom. However, the pathophysiological mechanism of PDVH, which is based on complex intercellular communication changes in the brain, has not yet been elucidated. Methods: We utilized multiple omics measurements and network-based approaches to address various intercellular communication changes in the brains of patients with PDVH. Results: Our non-target proteomics data revealed that the upregulation of protein module 2 was correlated with the progression of visual hallucinations. The pathological changes observed in PDVH were strongly associated with abnormalities in neurovascular coupling, confirmed by hemodynamic changes detected using transcranial Doppler ultrasound and functional magnetic resonance imaging. We further identified alpha-2-macroglobulin as the hub of endothelial dysfunction, which may trigger a cascade of neurovascular uncoupling and ultimately promote visual hallucinations in patients with Parkinson's disease. Conclusion: This study's findings shed light on a new approach for extracting biological insights from genetic association data and suggest a critical role for neurovascular uncoupling in the development of visual hallucinations in Parkinson's disease.

关键词

Parkinson's disease / visual hallucination / multi-omics / data modeling