Endothelial Degeneration of Parkinson's Disease is Related to Alpha-Synuclein Aggregation

Abstract

Objective: We previously reported that the ability of vascular remodelling is impaired in human Parkinson’s disease, leading to endothelial degeneration and vascular dysfunction. Aggregation of α-synuclein is a hallmark of neurodegeneration in Parkinson’s disease and inflammation and autophagy may contribute to secondary neuronal degeneration. The current study examined the association between these characteristic pathologies and endothelial cell degeneration in Parkinson’s disease. Methods: The study used the post-mortem grey matter from middle frontal gyrus (MFG) of human Parkinson’s disease and age-matched control cases. Immunohistochemical staining of phosphorylated α-synuclein, p62 for autophagy, Human Leukocyte Antigen-antigen D Related (HLA-DR) for activated microglia, Factor VIII for endothelial cells and Neuronal Nuclei for neurons were performed using either tissue microarray or free-floating sections. The expression of these factors were quantified by analysing the images of the stained sections and compared between the Parkinson’s disease and the age-matched control groups. Results: Compared to the control cases the expression of phosphorylated α-synuclein and p62 was increased in Parkinson’s disease, whereas both neurons and endothelial cells were significantly reduced, with no changes in the number of microglial cells. The density of phosphorylated α-synuclein was negatively correlated with the total length of endothelial cell associated blood vessels when compared across normal and Parkinson’s disease cases combined. However, using double label immunohistochemistry we found that the degree of endothelial cell degeneration in Parkinson’s disease was not directly related to the degree of neuronal degeneration and accumulation of phosphorylated α-synuclein. Conclusion: α-synuclein and autophagy are associated with endothelial degeneration in Parkinson’s disease. The degree of endothelial degeneration was not related to the extent of neuronal degeneration, both of which were copathological changes in PD brains. Alpha-synuclein-associated endothelial degeneration was also age-related pathology.