Brain Microvascular Endothelial Cell Derived Exosomes Potently Ameliorate Cognitive Dysfunction by Enhancing the Clearance of Aβ Through Up-Regulation of P-gp in Mouse Model of AD

Abstract

Accumulation of amyloid-β (Aβ) peptides in the brain is regarded as a major contributor to the pathogenesis and progression of Alzheimer's disease (AD). P-glycoprotein (P-gp) as a member of ABC transporter family situated in blood brain barrier (BBB) plays a role on cleaning of Aβ via its efflux transport effect in the treatment of AD. However, the expression of P-gp in pathological BBB was lower than that in normal BBB, thus impeding the clearance of Aβ. Here, we used human brain microvascular endothelial cells (HBMVECs) derived exosomes (HBMVECs-Ex) inheriting P-gp as an extracorporeal Aβ cleansing system to remove Aβ peptides from the brain by specific capture between P-gp and Aβ. The results showed that HBMVECs-Ex inheriting P-gp greatly facilitated the cerebral clearance of Aβ by effectively transporting Aβ out of brain and potently ameliorated cognitive dysfunction in AD mice. Taken together, HBMVECs-Ex provided a new strategy on the treatment of AD.

Keywords: Alzheimer’s disease; Amyloid-β; Blood–brain barrier; HBMVECs-Ex; P-glycoprotein.