Our results highlight the impact of AD on the anaplerotic (regeneration of metabolic intermediates) and cataplerotic (loss of metabolic intermediates to provide precursors for biosynthesis) nature of astrocytes and demonstrate how the delicate balance of maintaining neurotransmitter and metabolic demands could be perturbed in response to APP misprocessing in both acute and chronic exposure to Aβ. Here, APP is linked to Alzheimer disease.