title: Blood-brain barrier transport of circulating Alzheimer's amyloid beta.
abstract: The origin of amyloid beta (A beta) deposited in brain and cerebral blood vessels of patients with Alzheimer's Disease (AD) is not known. In this study, we tested whether soluble A beta (sA beta) can cross the blood-brain barrier (BBB). An in vivo vascular brain perfusion model and capillary depletion technique in guinea-pigs were used to determine cerebral capillary sequestration and blood-brain transport of a synthetic peptide identical with residues 1-40 (SP-40) of A beta. A saturable, specific binding of SP-40 has been demonstrated at the luminal side of the BBB, with the Kd of 25 +/- 2 nM, and Bmax of 188 +/- 11 fmol/min/g of isolated microvessels. A specific transcellular BBB transport of SP-40 into brain parenchyma exhibited the Km of 49 +/- 10 nM, and Vmax of 111 +/- 19 fmol/min/g of capillary depleted brain. We concluded that the BBB has the capability to control the cerebrovascular sequestration and blood-to-brain transport of circulating sA beta. Hence, sA beta can contribute to both cerebrovascular and parenchymal amyloid formation.
authors.affiliation: Department of Neurological Surgery, Childrens Hospital, Los Angeles, USC School of Medicine 90033.
authors.forename: B V
authors.initials: BV
authors.lastname: Zlokovic
authors.forename: J
authors.initials: J
authors.lastname: Ghiso
authors.forename: J B
authors.initials: JB
authors.lastname: Mackic
authors.forename: J G
authors.initials: JG
authors.lastname: McComb
authors.forename: M H
authors.initials: MH
authors.lastname: Weiss
authors.forename: B
authors.initials: B
authors.lastname: Frangione
mesh_terms: D016229:Amyloid beta-Peptides / Q000493:pharmacokinetics*; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002196:Capillaries / Q000502:physiology; D002250:Carbon Radioisotopes; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D008833:Microcirculation / Q000502:physiology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000493:pharmacokinetics; D013395:Sucrose / Q000493:pharmacokinetics
chemical_list: D016229:Amyloid beta-Peptides; D002250:Carbon Radioisotopes; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D013395:Sucrose