Aβ沉积仍然被认为是AD发病的主要原因，在AD发病过程中，减少Aβ沉积可能是预防AD发生的重要策略。血脑屏障由内皮细胞及星形胶质细胞等组成，在Aβ的外周转运中发挥关键作用，Aβ的外周转运下降可能是AD发病的原因。内皮细胞上的低密度脂蛋白受体相关蛋白1（LRP1）是Aβ的转运体，介导Aβ向外周转运。预实验结果表明：星形胶质细胞上的PirB可以和Aβ结合，引起VEGF的高表达；VEGF可以作用于内皮细胞而下调LRP1的表达。因此我们提出如下假说：1）Aβ与位于星形胶质细胞上的Aβ受体（PirB）结合；2）促进星形胶质细胞高表达VEGF；3）VEGF通过旁分泌作用于相邻的内皮细胞，引起Aβ转运体LRP1的表达下调；4）Aβ外周转运能力下降，引起神经元周围Aβ浓度相对增高沉积，参与AD的发生发展。我们拟通过体外血脑屏障模型及APP/PS1模型鼠探讨以上分子机制，为AD的提前预防提供理论与实验依据。

Beta-Amyloid (Aβ) deposition in the brain is still recognized as a major cause of Alzheimer’s disease (AD). Research shows gradual accumulation of Aβ might start decades prior to obvious AD symptom occurrence, thus the clearance of Aβ from brain is a key for prevention of AD. LRP1 is Aβ transporter on Blood-brain barrier (BBB), could deliver Aβ from brain side to blood side. Literatures and preliminary results demonstrate: Aβ could bind to PirB on astrocyte and induce high expression of VEGF; VEGF could act on endothelial cell and repress LRP1 expression and Aβ transport. Thus we hypothesize Aβ/PirB-VEGF-LRP1 pathway inhibits Aβ transport from brain to blood, and leads to deposition of Aβ in the cerebral tissue. Our research will deepen the understanding of AD pathogenesis; make theoretical innovation and new guide for AD prevention.