Abstract Amyloid β (Aβ) is a fibrillar component in Alzheimer′s disease amyloid deposits and a soluble peptide (sAβ) 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 sAβ. In this study, we examined whether two circulating amyloid-associated proteins shown to bind sAβ, 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 sAβ, sAβ 1-40. Brain perfusion experiments in guinea pigs showed significant uptake of both apo J and sAβ 1-40-apo J complexes. In contrast, blood-brain transport of sAβ 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 sAβ 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 sAβ transport.