Peripheral amyloid-beta levels regulate amyloid-beta clearance from the central nervous system.
Amyloid-beta (Abeta) is cleared from the brain by both proteolytic digestion and transport across the blood-brain-barrier into the peripheral circulatory system. To investigate the role peripheral Abeta levels play in regulating Abeta brain clearance, we measured the clearance of [125I]-Abeta(1-40) injected into the brains of liver-ligated rats that allowed peripheral Abeta levels to be maintained at elevated levels for approximately one hour with/without a single peripheral bolus of unlabeled Abeta(1-40). We found that elevating peripheral Abetalevels significantly decreased [125I]-Abeta(1-40) brain clearance, thus supporting the hypothesis that peripheral Abeta levels regulate Abeta clearance from the central nervous system.
Marques
Marcos A
MA
Geriatric Research, Education, and Clinical Center, Seattle, WA, USA.
Kulstad
J Jacob
JJ
Savard
Christopher E
CE
Green
Pattie S
PS
Lee
Sum P
SP
Craft
Suzanne
S
Watson
G Stennis
GS
Cook
David G
DG
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001693:Biological Transport, Active / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016229:Amyloid beta-Peptides; D007456:Iodine Isotopes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)