Research suggests that serum neurofilament light (NfL), an indirect measure of neuronal cell death, is associated with volumetric and white matter changes, and is predictive of cognitive decline in Alzheimer disease (AD). We report that NfL is associated with default mode network (DMN) functional connectivity as well as DMN connectivity with control networks. DMN connectivity with control networks is additionally associated with concurrent cognition. Hierarchical regression demonstrates NfL, DMN, and Aβ-amyloid each contribute to predicting cognition. These findings suggest NfL is an indirect marker of functional network degeneration and both NfL and DMN connectivity are distinct biomarkers of AD progression.