Approved research

Predicting Alzheimer's disease risk with polygenic and non-genetic risk factors.

Lay summary

Recent studies have found that an individual's genetic risk for late-onset Alzheimer's disease (AD) is determined by multiple genetic variants. We have recently developed a genetic score that combines the effects of these genetic variants into a single genetic score for predicting the age by which someone is likely to be diagnosed with AD dementia. However, genetic risk is only a single piece of the puzzle. Many individuals with high AD genetic risk do not eventually progress to AD dementia and many individuals with low AD genetic risk have been diagnosed with AD dementia. These findings suggest that beyond genetic risk, there are many other non-genetic risk factors such as cardiovascular disease, lifestyle, and mental health that contribute to brain atrophy and cognitive decline seen in the AD process. In this study, our aim is to investigate the complex relationships between genetic and non-genetic factors by elucidating how they may act independently or together to influence an individual's overall risk for AD-associated cognitive decline and brain atrophy. The project is expected to take up to three years at the first instance. We anticipate that the results from this study will identify and improve our understanding of the key non-genetic risk factors involved in the AD process. Modifying these non-genetic factors may be especially beneficial to individuals who are genetically predisposed to AD. In addition, a better understanding of the relationships between genetic and non-genetic risk factors may help inform the development of novel therapeutics strategies for treating AD. Preventive strategies and potential therapeutic drugs may be most effective in individuals with both high genetic risk and high modifiable non-genetic risk factors. Therefore, the findings of this project are likely to improve public health and impact clinical care of individuals with high AD risk.