The Role of LRP in Amyloid Deposition in APP/PS1 Mice

Project Summary

There is substantial evidence to suggest that the deposition of beta-amyloid (small fragments of a protein called the amyloid precursor protein) triggers a cascade of events that ultimately causes the symptoms of Alzheimer's disease. The life-long accumulation of amyloid peptide in the brain is determined by the rate of its generation versus clearance. A large number of studies have provided evidence that a protein called the low-density lipoprotein receptor-related protein (LRP) may play a pivotal role in regulating the production or clearance of amyloid peptides. In this study, we will use transgenic mouse models to study the roles of LRP in modulating amyloid pathology. We will use a genetic system, called Cre/lox, to eliminate LRP expression in specific types of cells in the forebrains of mice and then assess how this manipulation has altered amyloid deposition. It has been suggested that the binding of LRP to proteins involved in amyloid peptide production and clearance is the mechanism of action. If so, then it may be possible to identify drugs that modulate LRP binding to these proteins and thus influence its role in the formation of amyloid pathology.