The putative blood-brain barrier transporter for the β-amyloid binding protein apolipoprotein j is saturated at physiological concentrations

Abstract

beta-amyloid (A beta), the major component of the amyloid deposited in the brains of patients with Alzheimer's disease, is found in blood and can cross the blood-brain barrier (BBB). This suggests that the circulation could be a source of A beta in brain. The passage of unbound A beta across the BBB is slow. Most of the A beta in blood, however, is likely to be bound to apolipoprotein J (ApoJ). ApoJ and A beta bound to ApoJ have been shown to rapidly cross the BBB of the guinea pig when studied in situ with a blood-free brain perfusion model. ApoJ in blood, however, is found in a concentration 28 times higher than that needed to saturate the ApoJ transporter in situ. This suggests that the putative ApoJ transporter may not be functional in vivo. We found here that when measured in a murine in situ brain perfusion model, 125I-ApoJ crossed the BBB with a unidirectional influx rate constant (Ki) of 3.75 x 10(-3) ml/g-min, which is similar to that found in the guinea pig. After intravenous injection, however, no penetration of ApoJ across the BBB was measured in either the mouse or guinea pig. These results suggest that ApoJ is unlikely to provide a significant route for the transport of A beta across the BBB in vivo.