Aluminum complexing enhances amyloid beta 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 (Abeta), 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 Abeta (Abeta42) complexed with aluminum (Al-Abeta42) is much more cytotoxic than non-complexed Abeta42. The level of Abeta 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 Abeta to cross the in vivo BBB. We found that the rates of uptake of Al-Abeta42 and Abeta42 were similar, but that Al-Abeta42 was sequestered by brain endothelial cells much less than Abeta42 and so more readily entered the parenchymal space of the brain. Al-Abeta42 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-Abeta42 and Abeta42. In conclusion, complexing with aluminum affects some aspects of blood-to-brain permeability so that Al-Abeta42 would have more ready access to brain cells than Abeta42.
Banks
William A
WA
GRECC, Veterans Affairs Medical Center-St. Louis and Saint Louis University School of Medicine, Division of Geriatrics, Department of Internal Medicine, WAB, 915 N. Grand Blvd, St. Louis, MO 63106, USA. bankswa@slu.edu
Niehoff
Michael L
ML
Drago
Denise
D
Zatta
Paolo
P
D000465:Algorithms; D000535:Aluminum / Q000737:chemistry / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D051379:Mice; D008813:Mice, Inbred ICR; D012044:Regression Analysis
D000596:Amino Acids; D016229:Amyloid beta-Peptides; D000535:Aluminum