Vascularizing neurospheroids to probe vascular contributions to α-synuclein pathology in Parkinson's disease
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…
Parkinson's disease is increasingly linked to vascular dysfunction, but the role of vascular pathology in disease progression is not well understood. Researchers created a 3D model of brain tissue that included engineered neurospheroids and a self-assembled vascular network to better capture the neurovascular interface. By introducing preformed fibrils of α-synuclein into the engineered blood vessels, they were able to study the vascular contribution to Parkinson's disease pathology.
The results showed that exposing the vascular network to α-synuclein fibrils led to endothelial barrier disruption, vascular leakage, inflammation, and vascular regression. Importantly, this vascular damage also triggered intraneuronal aggregation of α-synuclein within the neurospheroids, indicating that vascular dysfunction may help expose neural tissue to pathogenic α-synuclein.
This new modeling approach provides a versatile platform for investigating how vascular issues can contribute to the progression of neurodegenerative diseases like Parkinson's.
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