Vascularizing neurospheroids to probe vascular contributions to α-synuclein pathology in Parkinson’s disease
Year: 2026
Type: preprint
Abstract: Neurodegenerative diseases are increasingly associated with vascular dysfunction beyond progressive neuronal degeneration, yet how vascular pathology contributes to disease progression remains poorly understood, largely due to the lack of a neurodegenerative disease model capable of capturing neuronal pathology alongside associated vascular dysfunction. Here, we developed a microengineered 3D vascularized brain tissue model that integrates neurospheroids with a self-assembled, perfusable vascular network to recapitulate key features of the neurovascular interface. Using this model, we investigated the vascular contribution to Parkinson's disease pathology by introducing α-synuclein preformed fibrils into the engineered vasculature. Intravascular α-syn fibril exposure induced endothelial barrier disruption, vascular leakage, inflammation, and vascular regression. Notably, this vascular insult was accompanied by intraneuronal α-synuclein aggregation within neurospheroids, suggesting that vascular dysfunction may facilitate the exposure of neural tissue to pathogenic α-synuclein. Our neurodegenerative disease modeling approach establishes a versatile and tractable platform for investigating vascular contributions to neurodegenerative disease progression.
Institutions: Binghamton University, Drexel University
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7204747151