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The mechanisms through which reduced EAAT2 expression contributes to cognitive decline and AD-related neurodegeneration and the differential functional roles of its astrocytic and neuronal components remain largely unknown. This study uses behavioral analysis to show that astrocytic and neuronal EAAT2 deficiency in mice causes age-dependent cognitive dysfunction. Furthermore, we show that gene expression from human AD and aging datasets have a robust overlap with astrocytic EAAT2 deficiency. 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