Microvascular Changes in Parkinson's Disease- Focus on the Neurovascular Unit

Vascular alterations emerge as a common denominator for several neurodegenerative diseases. In Parkinson's disease (PD), a number of observations have been made suggesting that the occurrence of vascular pathology is an important pathophysiological aspect of the disease. Specifically, pathological activation of pericytes, blood-brain barrier (BBB) disruption, pathological angiogenesis and vascular regression have been reported. This review summarizes the current evidence for the different vascular alterations in patients with PD and in animal models of PD. We suggest a possible sequence of vascular pathology in PD ranging from early pericyte activation and BBB leakage to an attempt for compensatory angiogenesis and finally vascular rarefication. We highlight different pathogenetic mechanisms that play a role in these vascular alterations including perivascular inflammation and concomitant metabolic disease. Awareness of the contribution of vascular events to the pathogenesis of PD may allow the identification of targets to modulate those mechanisms. In particular the BBB has for decades only been viewed as an obstacle for drug delivery, however, preservation of its integrity and/or modulation of the signaling at this interface between the blood and the brain may prove to be a new avenue to take in order to develop disease-modifying strategies for neurodegenerative disorders.

Automated summary

Vascular alterations are commonly observed in various neurodegenerative diseases, including Parkinson's disease (PD). This review examines the evidence for different vascular changes in PD patients and animal models, ranging from pericyte activation and blood-brain barrier (BBB) disruption to compensatory angiogenesis and vascular rarefaction. The review also highlights the potential role of perivascular inflammation and metabolic disease in these vascular alterations. Understanding the contribution of vascular events to PD pathogenesis could lead to the development of novel therapeutic strategies, such as modulating the BBB and its signaling at the interface between the blood and the brain.