INTRODUCTION: Functional connectivity within the medial temporal lobe (MTL) and default mode network (DMN) changes across Alzheimer's disease stages, influenced by and influencing cortical amyloid-beta (Aβ) and regional tau burden. Previous research highlights functional connectivity's role in Alzheimer's disease progression and the interactions of cortical Aβ and functional connectivity within and between the MTL and DMN, but their impact on regional tau deposition remains largely unexplored. METHODS: Cognitively unimpaired participants from OASIS-3 (AV1451 cohort, RESULTS: In Aβ- participants, lower "MTL Integration Axis" functional connectivity (PC1) was associated with higher tau levels in the left entorhinal cortex. In Aβ+ participants, lower "MTL Integration Axis" functional connectivity correlated with elevated tau levels in the DMN's left lateral parietal cortex, MTL's right parahippocampal cortex, and Braak stages 3-6 brain regions. DISCUSSION: Decreased functional connectivity was associated with increased regional tau burden, showing Aβ status-specific effects. Enhancing MTL functional connectivity could be a therapeutic strategy and a promising direction for future clinical interventions.