CDistribution and Regulation of the Amyloid Procursor of Alzheimer's (AD) (2011 - Present)

Investigator:  Joseph DeGiorgis, Providence College
Collaborator/Mentor:  John Marshall, Brown University 

Abstract:  Alzheimer's disease (AD) afflicts an estimated 26.6 million individuals worldwide, and the prevalence is predicted to increase to 100 million by 2050 at an estimated cost of 20 trillion dollars over the next 40 years to the US alone. Many familial forms of AD are caused by mutations in the Amyloid Precursor Protein. These mutation are inherited in an autosomal dominant pattern and lead to the loss of long-term memory, language degeneration, and cognitive impairment that characterize this disorder. APP is a transmembrane protein associated with membrane bound vesicles. While the N-terminus of the protein resides in the vesicle lumen the C-terminus extends from the vesicle membrane into the cytoplasm where it is thought to associate with kinesins, the plus end directed microtubule-based motors involved in intracellar transport. In addition, APP is found at the postsynaptic terminal where it is thought to facilitate synapse formation. We have recently identified a cyclic peptide that promotes the expression of APP. Here, we hope to determine whether APP and motor proteins co-localize at the organelle microtubule interface through an electron microscopy approach, as well as determine whether APP expression can be modulated by the cyclic peptide.