Investigator: David Tate, PhD
Project Title: Cardiac integrity and white matter abnormalities in mild cognitive impairment
This project cross-sectionally examines relations between heart function and white matter changes in the brain among elders with mild cognitive impairment MCI. Investigating these relations may provide insight into future prevention strategies for abnormal cognitive decline and dementia.
Investigator: Peter Morin, PhD
Project Title: Retromer and presenilin: Common endosomal functions in Alzheimer’s disease
In Alzheimer’s disease, amyloid plaques are formed from fragments of the amyloid precursor protein (APP). These fragments are generated within a cellular compartment known as the endosome. Current evidence suggests that the machinery that transports APP out of the endosome may be defective, causing APP to remain in this compartment where toxic Ab peptides are formed. We have recently identified a protein (VPS35) which is a component of an endosomal trafficking complex (retromer) that interacts with the Wnt receptor, Lrp6. We and others have shown that retromer function regulates APP metabolism and Wnt signaling. Presenilin 1, a familial Alzheimer’s disease gene, also regulates APP metabolism and Wnt signaling. Our Pilot studies are focused on understanding how Presenilin 1 and retromer transport affect APP metabolism and Wnt signaling in the endosome. By manipulating the expression of VPS35 and other endosomal proteins, we are probing endosomal functions relevant to APP metabolism and Wnt signaling. Understanding the cellular processes that cause amyloid formation may be important for development of rational treatment strategies.