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2008 Grants - Andersen
Influence on APP Processing by the Sorting Complex of SorLA and Retromer
Olav Andersen, Ph.D.
University of Aarhus
2008 New Investigator Research Grant
Amyloid precursor protein (APP) is the parent molecule of beta-amyloid, which is a key suspect in the pathology leading to Alzheimer's disease. Before it is cut to yield beta-amyloid, however, APP must be transported to specific compartments within the cell. SorLa and retromer are two key proteins in the cellular machinery that sort APP and control its transport (trafficking).
Levels of both sorLA and retromer in brain cells are known to be reduced in persons with Alzheimer's disease. This observation suggests that impaired sorting or trafficking of APP may cause excessive amounts of it to accumulate in compartments where it is processed into beta-amyloid, thereby leading to Alzheimer pathology. In agreement with this idea, Olav Andersen, Ph.D., and colleagues have found evidence that sorLA normally directs APP to cellular compartments where it is less likely to be processed into beta-amyloid.
Dr. Andersen and colleagues plan to perform additional studies of how sorLA and retromer control the trafficking of proteins in cells, especially the traf-ficking of APP. They plan to study how sorLA and retromer interact and how they identify and traffic other proteins. These studies will shed light on some of the earliest identified steps in the development of Alzheimer pathology.