Antecedent Biomarkers for Alzheimer Disease: The Adult Children Study

Overall: Project Summary/Abstract “Antecedent Biomarkers for Alzheimer Disease: The Adult Children Study” (ACS) will determine when during the lifespan molecular markers of Alzheimer disease (AD) appear in the brain of cognitively normal, largely middle-age individuals and also will characterize the course of preclinical AD. With maturation of the original ACS cohort, we now will identify the factors that mediate the transition from preclinical AD to symptomatic AD (the latter term in this application is used to encompass both mild cognitive impairment due to AD and AD dementia). This renewal application examines the hypothesis that disrupted neural integrity predicts the transition from preclinical to symptomatic AD and thus proposes four Cores (Administration, Clinical, Fluid Biomarker, and Data Management and Biostatistics) to support four Projects: Project 1 (JC Morris and T Benzinger, Co-Project Leaders), “Tau burden and spatial spread in preclinical Alzheimer disease”; Project 2 (AM Fagan, PL), “Plasma and cerebrospinal fluid (CSF) biomarkers that predict risk for symptomatic Alzheimer disease”; Project 3 (B Ances, PL), “Alzheimer disease progression, host gut microbiome, and enteric dysfunction”; and Project 4 (D Head, PL), “Mechanisms and moderators of the effects of physical activity in preclinical AD”. Although these Cores and Projects each address unique Specific Aims, they will generate a wealth of cross-sectional and longitudinal data from ACS participants to permit a cohesive and comprehensive examination of the overarching Aims of this renewal application. Hence, the ACS as a whole is far greater than the sum of its Cores and Projects.