<h4>Introduction</h4>The locus coeruleus (LC) is among the first sites of tau pathology in Alzheimer's disease (AD) and may seed neocortical tau.<h4>Methods</h4>We used longitudinal neuromelanin-sensitive MRI to assess LC integrity in vivo in a cohort of cognitively unimpaired older adults with familial risk of AD in relation to tau and amyloid positron emission tomography (PET) and long-term cognitive trajectories.<h4>Results</h4>We showed that both LC integrity at baseline and its rate of degeneration over time independently predicted a neocortical pattern of tau deposition. The gene discussed is MAPT; the disease is Alzheimer disease.