Passage of human amyloid beta-protein 1-40 across the murine blood-brain barrier.
Previous studies have suggested that the amyloid beta-protein present in the brains of patients with Alzheimer's disease may be derived in part from peripheral blood. We determined that after IV injection of synthetic amyloid beta-protein 1-40 (A beta), labeled with radioactive 125I (I-A beta), radioactivity accumulated in the brains of mice by a nonsaturable mechanism. Radioactivity also accumulated in the brain after the i.v. injection of radioiodinated reverse amyloid beta-protein 40-1 (I-rA beta). Capillary depletion techniques, however, showed I-A beta to have a much greater degree of association with brain capillaries than I-rA beta. Acid precipitation of radioactivity in CSF samples and recovery from cortical homogenates suggested the presence of intact I-A beta within the CNS after peripheral administration. HPLC analysis of cortical homogenates confirmed the presence of intact I-A beta. Gel electrophoresis of the CSF acid precipitates and of the HPLC fractions further verified the presence of intact blood-derived I-A beta peptide in CNS. These results suggest that endogenous bloodborne A beta can enter the CNS after associating with the capillary endothelium to accumulate intact within the parenchymal and CSF spaces of the brain.
Maness
L M
LM
Department of Neuroscience, Tulane University School of Medicine, New Orleans, Louisiana.
Banks
W A
WA
Podlisny
M B
MB
Selkoe
D J
DJ
Kastin
A J
AJ
D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002196:Capillaries / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010446:Peptide Fragments / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C090308:amyloid beta-protein (40-1)