Neuronal death is a hallmark of Alzheimer's disease (AD) and considerable work has been done to understand how the loss of interconnectivity between neurons contributes to the associated dementia. Often overlooked however, is how the loss of neuronal innervation of blood vessels, termed perivascular innervation, may also contribute to the pathogenesis of AD. There is now considerable evidence supporting a crucial role for the neurovascular unit (NVU) in mediating the clearance of the β-amyloid (Aβ) peptide, one of the main pathological constituents of AD, from the brain. Moreover, efficient removal appears to be dependent on the communication of cells within the NVU to maintain adequate vascular tone and pulsatility. This review summarizes the composition of the NVU, including the sources of perivascular innervation and how the NVU mediates Aβ clearance from the brain. It also explores evidence supporting the hypothesis that loss of neurally mediated vasoreactivity contributes to Aβ pathology in the AD brain.

1. We propose the following model of Ca 2+ mobilization by noradrenaline in vascular smooth muscle. Upon receptor occupation Ca 2+ from a labile small intracellular store on the inner plasmalemma is released. This Ca 2+ does not function as activator Ca 2+ but triggers Ca 2+ release from the sarcoplasmic reticulum (Ca 2+ -induced Ca 2+ release). 2. Simultaneously Ca 2+ from an extracellularly bound store (on the external surface of the plasmalemma) is dislodged, which enters the cell through receptor linked channels. 3. These processes are responsible for the early ‘phasic’ component of the noradrenaline contraction. In addition, Ca 2+ from the free extracellular Ca 2+ pool enters through receptor operated channels, supporting the maintained tension development.

1. The present study was undertaken to examine whether there is a kallikrein-like enzyme in vascular tissue. Isolated saline-perfused rat mesenteric arteries were used and arterial homogenate was incubated with heat-treated dog plasma and citrate/phosphate buffer (pH 8.5) in the presence of peptidase inhibitors for 60 min. 2. The kallikrein-like enzyme showed optimum activity in the range pH 7.0-9.0. The rate at which it releases kinin is similar to the release of kinin by kallikrein and trypsin. The release is unaffected by incubation of the enzyme with trypsin-inhibitors, but completely inhibited by aprotinin. 3. The kinin released by arterial homogenate resembles bradykinin in its chemical and pharmacological properties, and by using antibodies that specifically inhibit kinins, the biological action was completely abolished. 4. These results indicate that arterial tissue contains an enzyme with physicochemical characteristics quite similar to those of kallikreins of glandular origin.