Amyloid Beta-Mediated Neurovascular Toxicity in Alzheimer's Disease.

Abstract

The brain vascular system receives one-fifth of the total oxygen from the cardiac output, and this transport system is highly dependent on blood-brain barrier (BBB) integrity. The cerebral blood flow is controlled by neurovascular coupling through neurovascular units (NVUs). The NVU includes different types of cells, such as mural cells, astrocytes, pericytes, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs). The cellular composition of NVU varies throughout the vascular tree. Amyloid β (Aβ) is abundantly present in the central nervous system, but the pathological accumulation of misfolded Aβ protein causes vascular damage, resulting in neurovascular dysfunction. Aβ aggregation can activate the astrocytes and endothelial cells. It is followed by pericyte degeneration which results in dysregulation of cerebral blood flow (CBF), neurovascular uncoupling, and BBB breakdown. Thus, understanding the cellular and molecular mechanisms of Aβ-induced neurovascular toxicity is crucial for determining normal and diseased brain function. This chapter discusses the components of NVU, neurovascular uncoupling, Aβ-induced cerebrovascular reactivity, and cerebral blood flow reduction in neurodegenerative disorders, with special emphasis on Alzheimer's disease.