Project 1 explores the transition from asymptomatic, preclinical Alzheimer disease (AD) to symptomatic AD by incorporating the novel tau imaging tracer, T807 F18 (AV1451), into the biomarker-rich protocol of the Adult Children Study (ACS) to identify the temporal onset of neocortical involvement by tau and to quantify tau density and distribution. Project 1 findings will be correlated with other indicators of preclinical AD obtained in all Projects and relevant Cores of this application as described in the Specific Aims below. 1. Assess cerebral tau distribution and burden in the ACS, at baseline and longitudinally every three years thereafter, with T807 positron emission tomography (PET) imaging. a. Compare tau burden cross-sectionally in cognitively normal participants and those with symptomatic AD. b. Correlate cerebrospinal fluid (CSF) tau and p-tau181 (Biomarker Core, Project 2) with T807 to test the hypothesis: tauopathy-related neural injury predicts the transition from preclinical to symptomatic AD. c. Similarly, correlate the spatial distribution of tauopathy to test the hypothesis: the spread of tauopathy from the transentorhinal region to the neocortex predicts the transition from preclinical to symptomatic AD. 2. Correlate cross-sectional and longitudinal T807 imaging: a. With amyloid PET imaging (Project 4) to test the hypothesis that cerebral amyloidosis and tauopathy each are necessary to predict the transition to symptomatic AD. b. With CSF concentrations of tau, p-tau181, VILIP-1, SNAP-25, and Neurogranin (Biomarker Core, Project 2), as markers of synaptic and neural injury, and with CSF Aβ42 and YKL-40. c. With imaging measures of hippocampal atrophy, reduced cortical thickness, and disrupted resting state networks (Project 4) as markers of neural injury 3. Identify inflection points (changepoints) on composite measures of episodic memory (Clinical Core), attentional control (Project 3), and global cognitive performance (Clinical Core) that indicate the cognitive decline heralding the onset of symptomatic AD.