Aluminum complexing enhances amyloid β protein penetration of blood-brain barrier

A significant co-morbidity of Alzheimer's disease and cerebrovascular impairment suggests that cerebrovascular dysregulation is an important feature of dementia. Amyloid beta protein (A beta), a relevant risk factor in Alzheimer's disease, has neurotoxic properties and is thought to play a critical role in the cognitive impairments. Previously, we demonstrated that the 42mer of A beta (A beta 42) complexed with aluminum (Al-A beta 42) is much more cytotoxic than non-complexed A beta 42. The level of A beta in the brain is a balance between synthesis, degradation, and fluxes across the blood-brain barrier (BBB). In the present paper, we determined whether complexing with aluminum affected the ability of radioactively iodinated A beta to cross the in vivo BBB. We found that the rates of uptake of Al-A beta 42 and A beta 42 were similar, but that Al-A beta 42 was sequestered by brain endothelial cells much less than A beta 42 and so more readily entered the parenchymal space of the brain. Al-A beta 42 also had a longer half-life in blood and had increased permeation at the striatum and thalamus. Brain-to-blood transport was similar for Al-A beta 42 and A beta 42. In conclusion, complexing with aluminum affects some aspects of blood-to-brain permeability so that Al-A beta 42 would have more ready access to brain cells than A beta 42. (c) 2006 Elsevier B.V. All rights reserved.