Neurovascular regulation in the normal brain and in Alzheimer's disease

Key Points The rate of cerebral blood flow (CBF) is positively correlated with brain activity. This 'functional hyperaemia' is mediated by the coordinated action of various vasoactive agents — including ions that are associated with synaptic transmission and some neurotransmitters — on blood vessels. The increases in CBF that are associated with neural activity are spatially restricted to the site of activity. Local interneurons and astrocytes are probably crucial to regulation of CBF at this level, producing and releasing vasoactive mediators. Vasodilation of extracerebral arteries that supply the site of neural activity is probably achieved through the upstream transmission of vasoactive signals within the walls of blood vessels. The 'neurovascular unit' — a functional entity comprising neurons, astrocytes, smooth muscle cells and endothelial cells — has a key role in the haemodynamic response to brain activity. Disruption of this regulatory network occurs in response to brain injury; for example, during stroke. Evidence now indicates that cerebrovascular dysfunction is a feature of neurodegenerative disorders such as Alzheimer's disease. Accumulation of amyloid β-peptide (Aβ) in brain is associated with neuronal death in Alzheimer's disease. Aβ induces dysfunction in all cell types of the neurovascular unit and interferes with the function of blood vessels. These effects are mediated through reactive oxygen species.