BRAIN UPTAKE OF CIRCULATING APOLIPOPROTEIN-J AND APOLIPOPROTEIN-E COMPLEXED TO ALZHEIMERS AMYLOID-BETA

Amyloid beta (A beta) is a fibrillar component in Alzheimer's disease amyloid deposits and a soluble peptide (sA beta) normally present in body fluids, We have recently reported that the blood-brain barrier (BBB) has a capability to control cerebrovascular sequestration and transport of circulating sA beta. In this study, we examined whether two circulating amyloid-associated proteins shown to bind sA beta, apolipoproteins J (apo J) and E (apo E), can cross the BBB alone and/or complexed to a synthetic peptide homologous to a major form of sA beta, sA beta(1-40). Brain pel fusion experiments in guinea pigs showed significant uptake of both apo J and sA beta(1-40)-apo J complexes. In contrast, blood-brain transport of sA beta(1-40)-apo E was negligible, while apo E had a limited access across the BBB, indicating that the apo E found within the brain is produced locally. It is concluded that sA beta(1-40) binding to apo J and apo E results in significant (> 100-fold) difference in brain uptake of their respective complexes. We hypothesize that in normal brain apo J facilitates sA beta transport. (C) 1994 Academic Press, Inc.