P2‐347: Absence of MDR‐1 P‐glycoprotein at the blood‐brain barrier increased the passage of blood‐borne exogenous Aβ peptides across the BBB into the brain

• DOI: 10.1016/j.jalz.2010.05.1398
• Publication Date: 2010-07-12T00:07:34Z
• Authors: Wandong Zhang; Huaqi Xiong; Shanshan Shen; Aimee Jones; Peilin Huang; Howard Njoo; Jun Wu
• Keywords: P-glycoprotein; Pathogenesis; Ex vivo; Knockout mouse

Alzheimer's disease (AD) is characterized by accumulation and deposition of Aβ peptides in the brain. Experimental studies showed that can be transported across blood-brain barrier (BBB). Aberrant transport BBB may contribute to Some suggested mis-folded transmitted via transfusion from donors recipients, which a risk factor AD pathogenesis. Several transporters/receptors are involved BBB. MDR-1 P-glycoprotein/ABCB1 (Pgp) highly expressed cerebroendothelial cells acts as major drug transporter at Pgp was shown play substantial role elimination However, it unknown whether prevent blood-borne exogenous entering In present study, we investigated passage into Cy5.5-labeled Aβ1-40 or Cy5.5 free-dye were injected intravenously mdr-1a/b knockout (Pgp-null) wild-type (wt) mice. The mice scanned alive with time-domain optical imager eXplore Optix 2, 4, 6, 8h post-injection for fluorescence Mice sacrificed their ex vivo brains scanned. concentration heads Pgp-null higher 4 time-points than wt same amount (Pgp-null/wt mice: 2h: 124.61%/100%; 4h: 126.21%/100%; 6h: 116.03%/100%; 8h: 141.28%/100%). fluorescent brain also (109.33%) (100%). Two pairs either equal intensity 8h. two had about 1.5-fold intensity, suggesting easily trans-passed These results indicate absence increased