BLOOD-BRAIN-BARRIER UPTAKE OF THE 40-AMINO-ACID-SEQUENCE AND 42-AMINO-ACID-SEQUENCE OF CIRCULATING ALZHEIMERS AMYLOID-BETA IN GUINEA-PIGS

An intracarotid brain infusion/capillary depletion technique was used in guinea pigs to examine cerebral capillary sequestration and transpo rt 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 v ascular deposits, and the 42 residue form, found primarily in senile p laques. The peptides crossed well into the brain parenchyma via a spec ific transport mechanism for which sA beta(1-40)) had an approximately two-fold greater affinity than sA beta(1-42). There was significant c apillary sequestration of SA beta(1-40, but retention by the microvasc ulature 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 barrie r sequestration and transport of their respective circulating precurso rs.