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.
Martel
C L
CL
Department of Neurological Surgery, Childrens Hospital Los Angeles, USC School of Medicine 90033, USA.
Mackic
J B
JB
McComb
J G
JG
Ghiso
J
J
Zlokovic
B V
BV
D000544:Alzheimer Disease / Q000097:blood*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000097:blood*; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D006224:Cricetinae; D005260:Female; D008297:Male
D016229:Amyloid beta-Peptides