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

An intracarotid brain infusion/capillary depletion technique was used in guinea pigs to examine cerebral capillary sequestration and transport into brain parenchyma of sA beta(1-40) and sA beta(1-42), synthetic peptides identical to two forms of the amyloid beta 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 beta(1-40)) had an approximately two-fold greater affinity than sA beta(1-42). There was significant capillary sequestration of SA beta(1-40, but retention by the microvasculature of SA beta?(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.