Assessing the contributions of the genome and exposome on Alzheimer's disease and related dementias

The objective of the proposed research is to investigate genetic contributors to Alzheimer’s disease and related dementias (ADRD) and to develop genomic-informed approaches for personalized risk assessment using data from the Alzheimer’s Disease Sequencing Project (ADSP). The study will involve secondary analyses of existing genomic and phenotypic datasets generated through the ADSP. Planned analyses include the evaluation of polygenic and other genetic risk factors, the development and validation of integrated risk prediction models, and the assessment of relationships among genetic, clinical, and biomarker measures associated with ADRD risk and progression. Causal inference and mediation approaches may be used to examine pathways linking genetic susceptibility to ADRD-related outcomes. Available outcomes may include clinical diagnoses, cognitive and neuropsychological measures, neuropathological traits, biomarker data, and neuroimaging measures. Additional exploratory analyses may be conducted to identify factors that modify disease risk, progression, and heterogeneity across populations. The overall goal of this research is to improve understanding of genetic susceptibility to ADRD and support the development of more precise and personalized approaches to risk assessment.

Alzheimer's disease and related dementias affect millions of individuals and families worldwide, yet there is substantial variation in who develops these conditions and how they progress. This project will use data from the Alzheimer's Disease Sequencing Project to better understand how inherited genetic factors contribute to disease risk and progression. The research will examine how genetic information can be combined with other health-related information to improve the assessment of an individual's likelihood of developing dementia. By studying diverse populations and a range of disease-related measures, including memory and thinking abilities, brain imaging, and biological markers, this work aims to improve understanding of the factors that influence dementia risk. The long-term goal is to support more personalized approaches to identifying individuals at increased risk and to advance strategies for earlier detection and prevention of Alzheimer's disease and related dementias.