Modulation of Amyloid-β1-40 Transport by ApoA1 and ApoJ Across an in vitro Model of the Blood-Brain Barrier

Amyloid-beta (A beta) accumulation in Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) is likely caused by the impairment of its brain clearance that partly occurs through the blood-brain barrier (BBB). In this context, an in vitro BBB model is a valuable tool for studying the molecular mechanisms that regulate this process. This study assessed brain A beta elimination across the BBB and its modulation by the natural chaperones Apolipoprotein A1 (ApoA1) and Apolipoprotein J/Clusterin (ApoJ). The model was based on primary cerebral endothelial cells that were cultured on Matrigel-coated Transwells and treated with fluorescently labeled-A beta(1-40) to track its efflux across the BBB, which corresponds to trafficking from the basolateral (brain) to apical (blood) compartments. We observed that the transport of basolateral A beta(1-40) was enhanced when it was complexed to rApoJ, whereas the complex formed with rApoA1 did not influence A beta(1-40) efflux. However, the presence of rApoA1 in the apical compartment was able to mobilize A beta(1-40) from the basolateral side. We also observed that both rApoA1 and rApoJ moderately crossed the monolayer ( from blood to brain) through a mechanism involving the LDL receptor-related protein family. In contrast to the increased rApoJ efflux when complexed to A beta(1-40), rApoA1 trafficking was restricted when it was bound to the A beta peptide. In summary, the present study highlights the role of ApoJ and ApoA1 in the in vitro modulation of A beta elimination across the BBB.