Abstract
Related to the great importance of the intra-arterial perivascular drainage (IPAD), the drainage function of the lipoprotein receptor-related protein-1 (LRP1) that is a huge transmembrane LRP receptor member, is increasingly becoming the subject of comprehensive researches. Two important questions thus emerged: 1. How does the binding of the whole ligand complex members, among them amyloid beta (Aβ), the crucial factor in the pathology and pathophysiology of Alzheimer's disease (AD), lead to conformational changes in the extracellular receptor structure? 2. How do these changes reflect in the structure of the receptor intracellular tail, with the binding of PICALM (phosphatidylinositol binding clathrin assembly protein) to the YXXL tail motif, and how do they reflect in the recruitment of a number of signal proteins, and in the onset of PICALM/clathrin Aβ endocytosis, transcytosis and Aβ exocytosis into the capillary circulation? Both questions require an exact explanation. The profound insight into the available literature related to these events does not give a satisfactory explanation to these questions; consequently, the present knowledge of the AD pathophysiology requires additional comprehensive research. This study is not concerned with the details of the AD pathology and pathophysiology; it is primarily concerned with the problem of Aβ binding to the LRP1, with local conformational changes in the tail, and with the activators of Aβ transcytosis and Aβ exocytosis into the capillary blood.
