Interactions of beta-amyloids with the blood-brain barrier.
Blood-borne beta-amyloids (A beta s) could affect brain function by (1) crossing the BBB to directly interact with brain tissues or (2) altering BBB function by interacting with the brain capillaries that make up the BBB. Several radioactively labeled A beta s have been examined for such interactions. Blood-borne A beta 1-28 is hindered from accumulating in brain by a slow rate of passage across the BBB and by robust enzymatic degradation. A beta 1-40, but not A beta 40-1 or A beta 1-42, is sequestered by brain capillaries, raising the possibility that it could affect BBB function. Small amounts of circulating A beta 1-40 are recovered intact from CSF and brain. A beta 1-40 is degraded by aluminum-sensitive, calcium-dependent intracellular enzymes. Apo-J, which can bind A beta, has been shown with an in situ method to be transported by a saturable system across the BBB. However, our recent work has shown that this system is not operable in vivo, probably because the transporter is saturated at physiological blood levels. In conclusion, A beta s have been shown to interact with and to cross the BBB.
Banks
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WA
Veterans Affairs Medical Center-New Orleans, Louisiana 70146, USA. bbbpts@mailhost.tcs.tulane.edu
Kastin
A J
AJ
Maness
L M
LM
Banks
M F
MF
Shayo
M
M
McLay
R N
RN
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001053:Apolipoproteins / Q000378:metabolism; D001692:Biological Transport; D001812:Blood-Brain Barrier; D006801:Humans
D016229:Amyloid beta-Peptides; D001053:Apolipoproteins