The pericyte: a forgotten cell type with important implications for Alzheimer's disease?

Pericytes are cells in the blood-brain barrier (BBB) that degenerate in Alzheimer's disease (AD), a neurodegenerative disorder characterized by early neurovascular dysfunction, elevation of amyloid β-peptide (Aβ), tau pathology and neuronal loss, leading to progressive cognitive decline and dementia. Pericytes are uniquely positioned within the neurovascular unit between endothelial cells of brain capillaries, astrocytes and neurons. Recent studies have shown that pericytes regulate key neurovascular functions including BBB formation and maintenance, vascular stability and angioarchitecture, regulation of capillary blood flow, and clearance of toxic cellular by-products necessary for normal functioning of the central nervous system (CNS). Here, we review the concept of the neurovascular unit and neurovascular functions of CNS pericytes. Next, we discuss vascular contributions to AD and review new roles of pericytes in the pathogenesis of AD such as vascular-mediated Aβ-independent neurodegeneration, regulation of Aβ clearance and contributions to tau pathology, neuronal loss and cognitive decline. We conclude that future studies should focus on molecular mechanisms and pathways underlying aberrant signal transduction between pericytes and its neighboring cells within the neurovascular unit, that is, endothelial cells, astrocytes and neurons, which could represent potential therapeutic targets to control pericyte degeneration in AD and the resulting secondary vascular and neuronal degeneration.