Apolipoprotein E Isoforms and Amyloid Beta Metabolism

Philip Verghese, PhD Washington University, School of Medicine


David Holtzman, MD Washington University


Apolipoprotein E appears to influence Alzheimer's disease pathogenesis in large part due to its ability to modulate amyloid-beta metabolism and structure. This ultimately influences the probability of amyloid beta aggregation. Our goal is to understand how apoE isoforms and lipid modulating molecules like ATP-binding cassette transporter A1 (ABCA1) take part in amyloid beta metabolism in the brain.

Project Details

Alzheimer's disease affects millions of people around the globe and the impact of this disease on society as a whole is enormous. Thus, it is necessary that we understand the cause of Alzheimer's disease and develop successful treatments. There is substantial evidence that the build-up of a small protein called amyloid beta in the brain produces a flow of events that drive brain cell collapse and ultimately causes Alzheimer's disease. Our research lab and others identified two important proteins called apolipoprotein E and ATP-binding cassette transporter A1 that, together, somehow influence amyloid beta production and breakdown. This eventually affects the likelihood of amyloid beta buildup in the brain. But we do not currently know the details of how these proteins control this amyloid beta buildup. So we are asking two important questions in order to understand the role of apolipoprotein E and ATP-binding cassette transporter A1 in amyloid beta production and breakdown. Our aims for this project are 1) study the factors that facilitate the binding of apolipoprotein E and amyloid beta 2) study how ATP-binding cassette transporter A1 controls the amyloid beta production and breakdown through apolipoprotein E proteins. The understanding of the connection between apolipoprotein E, amyloid beta and ATP-binding cassette transporter A1 will reveal additional ways that may be of therapeutic benefit in Alzheimer's disease.