INTRODUCTION: We investigated the hypothesis that tau burden in the locus coeruleus (LC) correlates with tau accumulation in cortical regions according to the Braak stages and examined whether the relationships differed according to cortical amyloid beta (Aβ) deposition. METHODS: One hundred and seventy well-characterized participants from an ongoing cohort were included. High-resolution T1, tau positron emission tomography (PET), and amyloid PET were obtained. RESULTS: LC tau burden was significantly linked to global tau in neocortical regions, as was tau in both early Braak stage (stage I/II) and later Braak stage areas. This relationship was significant only in Aβ-positive individuals. While LC tau did not directly impact memory, it was indirectly associated with delayed memory through mediation or moderation pathways. DISCUSSION: The findings from living human brains support the idea that LC tau closely relates to subsequent cortical tau accumulation, particularly among individuals with pathological Aβ accumulation, and identify LC tau burden as a promising indicator of cognitive trajectories of AD. HIGHLIGHTS: Tau burden in the LC was significantly associated with cortical tau accumulation. Tau burden in SN or PPN showed no association with cortical tau accumulation. LC tau burden was serially associated with Braak stages. The tau-LC and cortical tau relationship was significant only in the Aβ-positive group. Cortical amyloid's impact on memory worsens with higher tau accumulation in the LC.