CryoEM used for Alzheimer’s disease research
The Hormel Institute’s CryoEM microscope will soon be used for a new area of research – Alzheimer’s disease. Dr. Amer Alam, head of the Structural Biology of Membrane Transport lab at The Hormel Institute, has received a $435,750 2-year grant from the NIH Institute of Aging to study a specific protein, its effects on Alzheimer’s disease, and its possible use in future Alzheimer’s treatments.
Alzheimer’s disease represents one of the most important current healthcare challenges and is a leading cause of death worldwide. Alzheimer’s disease accounts for the overwhelming majority of dementias, which affect over 35 million people worldwide. This number is expected to double every twenty years.
Dr. Alam’s Alzheimer’s disease research focuses on a protein called Adenosine triphosphate (ATP) Binding Cassette Subfamily A member 7 (ABCA7) that transports molecules across cell membranes. Dysfunction of ABCA7 has been linked to both early and late onset Alzheimer’s disease through alterations in lipid homeostasis, Amyloid-Beta (Aβ) homeostasis, and phagocytosis. ABCA7 single nucleotide polymorphisms, or genetic variations, have been associated with late onset Alzheimer’s disease, suggesting that targeting ABCA7 could pave the way forward for new therapeutic Alzheimer’s disease strategies.
“Our results will shed light on the physiological functioning of human ABCA7, which is as of yet poorly understood, and validate its potential utilization as a therapeutic target for which future antibody and drug discovery efforts can be directed, thereby bridging basic and translational research for this relatively unexplored area of AD research,” shared Dr. Alam.
The long-term objectives of Dr. Alam’s research project are to gain insight into how human ABCA7 (hABCA7) looks and how it works. He and his team will use a combination of high-resolution structural analysis, in vitro functional characterization, and discovery of antibody and small molecule binders for hABCA7. The latter will aid in diagnostics and targeting, or function as potentiators and/or correctors of hABCA7 dysfunction.
The Hormel Institute’s CryoEM was added as part of the 2016 expansion. It is one of the world’s most powerful microscopes and allows scientists to see the structure of some of the smallest parts of our bodies – down to the near-atomic level. In this research project, the CryoEM will be used to create a detailed analysis of hABCA7 by itself and while it interacts with different molecules and lipid environments.