169 Objectives There is evidence that amyloid burden (Aβ) alters functional connectivity (FC; resting BOLD MRI) in subjects with Alzheimer’s Disease and Mild Cognitive Impairment and in elderly controls. We extended these studies by examining the relationship between Aβ and FC in a large lifespan sample of healthy controls (Dallas Lifespan Brain Study). Methods FC was measured in a continuous age sample of healthy adults (N = 137; 30-89 years old), as z-score-normalized temporal correlation coefficients. Seeds in posterior cingulate represented the Default Mode Network (DMN) and in anterior cingulate represented the Salience Network (SN). Participants had PET with 18Florbetapir to measure Aβ. SUVR (normalized to cerebellum) from a precuneus ROI was used for these analyses. Relationships between Aβ and fcMRI in DMN and SN were examined as continuous variables and by contrasting subjects with high Aβ against an age- and gender-matched group of low Aβ subjects (N=25 each). Results Precuneus Aβ was associated with decreased DMN connectivity in right precuneus and left orbital frontal cortex and increased connectivity in superior middle cingulate, and left medial and lateral peri-sylvian temporal lobe. SN connectivity was minimally reduced by precuneus Aβ, but substantially increased in bilateral insula, inferior striatum (near nucleus accumbens), hippocampus and dorsolateral prefrontal cortex. Between-group comparisons (high vs. low Aβ) revealed significant decreases in frontal connectivity associated with elevated Aβ in the DMN, while increased lateral temporal and insular connectivity was seen in the SN. Conclusions Increasing amyloid burden exerts negative effects on functional connectivity such that the DMN is less connected with increasing Aβ and SN connectivity is inappropriately increased. Research Support Supported by NIH grants 5R37AG-006265-25, 3R37AG-006265-25S1, and Alzheimer’s Association grant IIRG-09-135087. Radiotracer was generously provided by Avid Radiopharmaceuticals