Objective: To examine default mode and salience network functional connectivity as a function of APOE ε4 status in a group of cognitively normal age-, sex-, and education-matched older adults. Design: Case-control study. Subjects: Fifty-six cognitively normal APOE ε4 carriers and 56 age-, sex- and education-matched cognitively normal APOE ε4 noncarriers. Main Outcome Measure: Alterations in in-phase default mode and salience network connectivity in APOE ε4 carriers compared with APOE ε4 noncarriers ranging from 63 to 91 years of age. Results: A posterior cingulate seed revealed decreased inphase connectivity in regions of the posterior default modenetwork that included the left inferior parietal lobe, left middle temporal gyrus, and bilateral anterior temporal lobes in the ε4 carriers relative to APOE ε4 noncarriers. An anterior cingulate seed showed greater in-phase connectivity in the salience network including the cingulate gyrus, medial prefrontal cortex, bilateral insular cortex, striatum, and thalamus in APOE ε4 carriers vs noncarriers. There were no groupwise differences in brain anatomy. Conclusions: The observation of functional alterations in default mode and salience network connectivity in the absence of structural changes between APOE ε4 carriers and noncarriers suggests that alterations in connectivity may have the potential to serve as an early biomarker.