Blood-brain barrier uptake of the 40 and 42 amino acid sequences of circulating Alzheimer's amyloid β in guinea pigs

Abstract

An intracarotid brain infusion/capillary depletion technique was used in guinea pigs to examine cerebral capillary sequestration and transport into brain parenchyma of sA β 1–40 and sA β 1–42, synthetic peptides identical to two forms of the amyloid β peptide found in Alzheimer's disease lesions: the 40 residue form, found primarily in vascular deposits, and the 42 residue form, found primarily in senile plaques. The peptides crossed well into the brain parenchyma via a specific transport mechanism for which sA β 1–40 had an approximately two-fold greater affinity than sA β l–42 . There was significant capillary sequestration of sA β 1–40, but retention by the microvasculature of sA β 1–42 was negligible. These data suggest that the level of the 40 residue peptide in cerebral vasculature and of the 42 residue peptide in parenchyma could be regulated by blood-brain barrier sequestration and transport of their respective circulating precursors.