Ketone Bodies Promote Amyloid-β Clearance in a Human in Vitro Blood-Brain Barrier Model.

["Alzheimer's disease (AD) is characterized by the abnormal accumulation of amyloid-\u03b2 (A\u03b2) peptides in the brain. The pathological process has not yet been clarified, although dysfunctional transport of A\u03b2 across the blood-brain barrier (BBB) appears to be integral to disease development. At present, no effective therapeutic treatment against AD exists, and the adoption of a ketogenic diet (KD) or ketone body (KB) supplements have been investigated as potential new therapeutic approaches. Despite experimental evidence supporting the hypothesis that KBs reduce the A\u03b2 load in the AD brain, little information is available about the effect of KBs on BBB and their effect on A\u03b2 transport. Therefore, we used a human in vitro BBB model, brain-like endothelial cells (BLECs), to investigate the effect of KBs on the BBB and on A\u03b2 transport. Our results show that KBs do not modify BBB integrity and do not cause toxicity to BLECs. Furthermore, the presence of KBs in the culture media was combined with higher MCT1 and GLUT1 protein levels in BLECs. In addition, KBs significantly enhanced the protein levels of LRP1, P-gp, and PICALM, described to be involved in A\u03b2 clearance. Finally, the combined use of KBs promotes A\u03b2 efflux across the BBB. Inhibition experiments demonstrated the involvement of LRP1 and P-gp in the efflux. This work provides evidence that KBs promote A\u03b2 clearance from the brain to blood in addition to exciting perspectives for studying the use of KBs in therapeutic approaches."]