Objective: Parkinson’s disease is a movement disorder characterised by α-synuclein deposition in the form of Lewy bodies and Lewy neurites. Vascular changes have been thought to contribute to the neurodegeneration which underlies PD.

Background: Parkinson’s disease (PD) is characterised by α-synuclein accumulation in the form of Lewy pathology in the substantia nigra (SN). Cerebral hypoperfusion of the visual cortex has been reported in PD and associates with visual hallucinations, although the cellular mechanism/s have not been identified. We investigated regional changes in the vasculature in PD cases with variable disease durations. Specifically, we assessed the presence of string vessels, which are non-functional thin tissue fragments composed of collapsed basement membrane.

Method: We performed collagen IV immunohistochemistry on 10µm formalin-fixed, paraffin-embedded tissue sections from the SN, visual cortex and hippocampus of long (n=10) and short disease duration (n=8) PD cases compared to controls (n=7). Both total capillary length and percentage of string vessels were quantified using Image J.

Results: No difference in age at death, post-mortem delay or capillary length was seen between groups (p=>0.05). Increased string vessel formation was observed in the SN of all PD cases (p= <0.001). String vessels were increased in the visual cortex despite an absence of Lewy pathology in long (p= 0.01) (Braak IV-VI) but not short disease duration cases (p= >0.05) (Braak IV-V). Interestingly, no changes in string vessel formation were observed in the hippocampus in any group.

Conclusion: Our data demonstrates regional variations in string vessel formation in PD. String vessel formation in the visual cortex is present in cases with advanced disease stage, when visual hallucinations are common, and may underlie cortical hypoperfusion. Our findings suggest a significant vascular component to the pathogenesis of PD, which may be amenable to therapeutic intervention. 

String vessel formation regionally increases in long duration Parkinson’s disease [Conference presentation]. The 6th Annual Macquarie Neurodegeneration Meeting, Sydney, Australia. 14th September 2023.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/string-vessel-formation-regionally-increases-in-long-duration-parkinsons-disease/