Blood-brain barrier impairment in neurodegeneration

Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD) are the most widely studied neurodegenerative diseases. Although these diseases differ clinically and pathologically, they share some features. For example, neuronal death in these diseases occurs due to the accumulation of pathological proteins: amyloid  (A) in AD, -synuclein in PD and huntingtin in HD. Neuronal death in turn induces neuroinflammation, which is characterized by the activation of microglia and astrocytes, production of cytokines and nitric oxide, induction of oxidative stress, and migration of inflammatory cells to the central nervous system (CNS). These processes disrupt the blood-brain barrier (BBB), which is needed to maintain CNS homeostasis. The BBB is built by closely connected endothelial cells of the CNS capillaries, which, together with pericytes, are covered with a layer of basal membrane. Under physiological conditions, the BBB controls the migration of immune cells and the exchange of chemical compounds between the blood and the brain. Loss of BBB integrity in neurodegenerative diseases can worsen brain damage. A better understanding of the mechanisms of neurodegenerative diseases should improve the diagnosis and help find new treatment targets. In this article we present the structure and function of the BBB, including examples of BBB damage in AD, PD and HD.