Leveraging Heterogeneity in Alzheimer's Disease to Assess Differences in Longitudinal Health Outcomes

Abstract While it is generally recognized that many genetic and environmental factors contribute to Alzheimer''s disease (AD), current research efforts treat AD as a single disease. The extent to which heterogeneity among AD cases hinders our capacity to understand its etiology remains unclear. Therefore, there exists a critical need to examine genetic and phenotypic differences among AD cases to identify individuals with fundamentally different etiologies. Our overall objective is to evaluate etiological differences in AD cases and identify subtypes of the disease that have different health trajectories. We will characterize etiologically distinct subtypes of AD cases by evaluating health outcomes within and between subtypes. Our central hypothesis is that combinations of biomarkers and genetics significantly differ between individuals with AD, allowing for subtype classification. The rationale underlying this proposal is that AD is classified on a spectrum of neurodegeneration, and some individuals experience faster cognitive decline.