Identifying the Molecular Connections Between Cardiometabolic Problems and Alzheimer’s Disease

The goal of this project is to better understand the biology connecting cardiometabolic problems (like high blood pressure or cholesterol levels) and Alzheimer’s disease, specifically through studying the metabolites, proteins, and genes linking these conditions.

The underlying cause of Alzheimer’s disease is unknown, but there is ample evidence that certain cardiovascular problems may increase the risk. The goal of this project is to discover the key proteins and other molecules that connect these cardiovascular risk factors to Alzheimer’s disease by using data from some of the largest human studies available. At the completion of this project, we plan to follow up on our findings by testing whether these molecules can be used to improve how we diagnose or treat people with Alzheimer’s disease.

The goal of Aim 1 is to understand the molecular connections between certain blood tests (like lipid or cholesterol levels) and Alzheimer’s disease risk. The goal of Aim 2 is similar to Aim 1 but instead it focuses on cardiometabolic conditions and Alzheimer’s disease (including neurodegenerative biomarkers). The goal of Aim 3 is to find which cardiometabolic conditions appear to have a causal effect on Alzheimer’s disease risk, rather than a more coincidental relationship. By using genetics from large-scale population biobank data, we can test these causal relationships to understand better how cardiometabolic health relates to Alzheimer’s disease.

The innovation of this proposal is in the combination of scope and detail. Many different cardiometabolic conditions and measures will be studied, giving us a broad survey of metabolic and cardiovascular health in Alzheimer’s disease. At the same time, we will study thousands of different molecules, giving us a detailed look into the molecular landscape of these cardiometabolic risk factors.