‘Sink effect’ of dually-decorated nanoliposomes on Abeta clearance

F. Re, S. Minniti, L. Bana, M. Masserini, F. Re
University Milano Bicocca, IT

Keywords: Alzheimer’s disease, nanoliposomes, abeta, blood-brain barrier


Plaques containing beta-amyloid peptides are one of the hallmarks of Alzheimer’s disease (AD) and the reduction of Abeta is considered a primary therapeutic target. Recently, strategies have been employed to reduce Abeta brain levels and one of them is based on the ‘sink effect’ hypothesis, that is the peripheral administration of Abeta binding agents able to reduce Abeta brain amount by sequestering it in the plasma. This study for the first time investigates the potential effect of dually-decorated nanoliposomes (NL) on the Abeta exchange across an in vitro model of the blood-brain barrier (BBB). We observed that NL composed of sphingomyelin/cholesterol/phosphatidic acid and surface decorated with human ApoE-derived peptide strongly enhanced the basolateral-to-apical passage of Abeta across the BBB model (+110%). The rate of NL-mediated Abeta clearance was time- and lipid dose-dependent. NL and Abeta treatment did not affect the BBB functional and bioelectrical properties. This study provide rationale for the use of Abeta-binding NL as a treatment strategy in AD, by sequestering plasma Abeta.