Aluminum complexing enhances amyloid ? 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 β protein (Aβ), 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 Aβ (Aβ42) complexed with aluminum (Al-Aβ42) is much more cytotoxic than non-complexed Aβ42. The level of Aβ 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 Aβ to cross the in vivo BBB. We found that the rates of uptake of Al-Aβ42 and Aβ42 were similar, but that Al-Aβ42 was sequestered by brain endothelial cells much less than Aβ42 and so more readily entered the parenchymal space of the brain. Al-Aβ42 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-Aβ42 and Aβ42. In conclusion, complexing with aluminum affects some aspects of blood-to-brain permeability so that Al-Aβ42 would have more ready access to brain cells than Aβ42.