Blood brain barrier dysfunction in healthy aging and dementia: Why, how, what for?

The blood brain barrier (BBB) is an indispensable structure that maintains the central nervous system (CNS) microenvironment for a correct neuronal function. It is composed by highly specialized microvessels, surrounded by astrocytes, pericytes, neurons and microglia cells, which tightly control the influx and efflux of substances to the brain parenchyma. During aging, the BBB becomes impaired, and it may contribute to the development of neurodegenerative and neurological disorders including Alzheimer's disease and other dementias. Restoring the BBB can be a strategy to prevent disease onset and development, reducing the symptoms of these conditions. This work critically reviews the major mechanisms underlying BBB breakdown in healthy and unhealthy aging, as well as biomarkers and methodologies that accurately assess its impairment. Complementarily, potential therapeutic targets are discussed as new strategies to restore the normal function of the BBB in aging.