Service interruption on Monday 11 July from 12:30 to 13:00: all the sites of the CCSD (HAL, Epiciences, SciencesConf, AureHAL) will be inaccessible (network hardware connection).
Skip to Main content Skip to Navigation
Journal articles

Ketone Bodies Promote Amyloid-β1–40 Clearance in a Human in Vitro Blood–Brain Barrier Model

Abstract : Alzheimer's disease (AD) is characterized by the abnormal accumulation of amyloid-β (Aβ) peptides in the brain. The pathological process has not yet been clarified, although dysfunctional transport of Aβ 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 Aβ load in the AD brain, little information is available about the effect of KBs on BBB and their effect on Aβ 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 Aβ 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 Aβ clearance. Finally, the combined use of KBs promotes Aβ efflux across the BBB. Inhibition experiments demonstrated the involvement of LRP1 and P-gp in the efflux. This work provides evidence that KBs promote Aβ clearance from the brain to blood in addition to exciting perspectives for studying the use of KBs in therapeutic approaches.
Document type :
Journal articles
Complete list of metadata
Contributor : Virginie Justin-Labonne Connect in order to contact the contributor
Submitted on : Friday, December 31, 2021 - 10:36:30 AM
Last modification on : Friday, January 21, 2022 - 3:32:37 AM
Long-term archiving on: : Friday, April 1, 2022 - 6:36:52 PM


Versele et al., 2020.pdf
Publication funded by an institution


Distributed under a Creative Commons Attribution - NonCommercial 4.0 International License




Romain Versele, Mariangela Corsi, Andrea Fuso, Emmanuel Sevin, Rita Businaro, et al.. Ketone Bodies Promote Amyloid-β1–40 Clearance in a Human in Vitro Blood–Brain Barrier Model. International Journal of Molecular Sciences, MDPI, 2020, 21 (3), pp.934. ⟨10.3390/ijms21030934⟩. ⟨hal-02538226⟩



Record views


Files downloads