# Neurovascular dysfunction in the development and progression of neuroinflammatory diseases

## TL;DR

This paper reviews how dysfunction in the neurovascular unit contributes to various neurodegenerative diseases by disrupting the blood-brain barrier and causing inflammation.

## Contribution

The paper provides a comprehensive review of immune-mediated mechanisms in neurovascular dysfunction across multiple neurodegenerative diseases.

## Key findings

- Neurovascular unit disruption is linked to immune-driven vascular inflammation in Multiple Sclerosis.
- Protease-mediated tight junction degradation is observed in ischemic stroke.
- Endothelial dysfunction associated with α-synuclein is implicated in Parkinson’s Disease.

## Abstract

The neurovascular unit (NVU) is critical for brain homeostasis through its roles in maintenance of an effective blood brain barrier (BBB) and regulation of cerebral blood flow. Perturbation of the NVU is a hallmark of the pathology of multiple neurodegenerative diseases resulting in loss of BBB integrity, neuroinflammation and neuronal dysfunction. The NVU is a complex structure composed of endothelial cells, pericytes, as well as central nervous system (CNS) glial and neuronal components. While the importance of the CNS vasculature in health and disease is well established, the mechanisms underlying vascular pathology and its contributions to neurodegenerative diseases are less well defined. Neuroinflammation and reactive gliosis occurs in the majority of neurodegenerative diseases and recent studies suggest that immune mediated disruption of the BBB contributes to the induction of reactive gliosis and neuronal dysfunction. Potential consequences of NVU disruption include immune-driven vascular inflammation and leukocyte infiltration in Multiple Sclerosis (MS), protease-mediated tight junction degradation in ischemic stroke (IS), α-synuclein–associated endothelial dysfunction in Parkinson’s Disease (PD), amyloid-β– and tau-induced pericyte injury in Alzheimer’s Disease (AD), and complement-mediated vascular damage in Amyotrophic Lateral Sclerosis (ALS). Here we review the nature of NVU perturbations in these common neurodegenerative diseases, with an emphasis on the contribution of immune modulation of BBB disruption in neuropathology and disease progression.