Using genetic data to identify early determinants and causal environmental risk factors for Alzheimer’s disease

Background: Genetic studies have identified genetic risk variants associated with Alzheimer’s disease (AD) and with many other diseases and environmental exposures. Hypothesis: Genetic epidemiological studies using these genetic risk variants will improve understanding of causal links between AD, other diseases and environmental exposures. Methods: We will use data from large epidemiological studies to explore a) the genetic overlap between AD and early determinants of disease in children from the general population, and b) Mendelian randomization studies of causal effects of environmental exposures on AD. Anticipated outcomes for dementia: This project will enhance our causal understanding of the aetiology of AD and hence provide insight into potentially effective prevention and screening interventions.

There are 24 million people living with Alzheimer’s disease in the world and this number is expected to double in the next 20 years. Although there have been great advances in understanding the genetic factors involved in Alzheimer’s, there are still no confirmed environmental factors that can be targeted to reduce risk of Alzheimer’s in the population. Utilizing the existing information generated by genetic studies offers the opportunity to identify if there are risk factors that are not only associated with Alzheimer’s but are also causing an increased risk for it. We aim to use data from large general population studies to study if the same genetic factors that are involved in Alzheimer’s are also associated with early determinants of the disease in children and if certain environmental exposures are causing Alzheimer’s. For this, we will use rapid high-throughput analysis methods that we have developed to take advantage of publicly available information on the genetics of Alzheimer’s and risk factors for Alzheimer’s. Our project has the potential to improve understanding of the causes of Alzheimer’s and provide insight into potentially effective prevention and screening interventions.