Alzheimer´s disease (AD) is one of the main neurodegenerative disorders of the 21st century, characterized by a progressive decline in cognitive function. One important mechanism in memory formation and learning is adult neurogenesis, the process by which new neurons arise from dentate neural stem cells (NSCs). Current research of our group suggests that NSCs are affected in their fate decisions by AD. We observed an increased proliferation of NSCs in the pre-plaque phase which is followed by a strong decline in the number of NSCs and adult neurogenesis. Factors modulating NSC proliferation during adulthood and ageing are not well understood, however, our own preliminary data suggest that the loss of the co-transporter NKCC1 in NSCs alters proliferation behavior. The cation-chloride co-transporters NKCC1 and KCC2 are important modulators of intracellular chloride homeostasis and thus of the GABAergic system. The aim of the present study was to investigate the underlying mechanisms of early-onset of stem cell proliferation in AD. To this end, we quantified the expression levels of NKCC1 and KCC2 in hippocampal neural NSCs in young and middle-aged Nestin-GFP mice and APPxPS1/Nestin-GFP triple-transgenic mice. During ageing, levels of the NKCC1 co-transporter significantly decreased in the Nestin+ NSCs. Importantly, this age-related decrease was already seen in the AD animals in the pre-plaque phase. On the contrary, in the aged stem cells the KCC2 co-transporter was increased Our results suggest that alteration of NKCC1 and KCC2 play an important role in the early overactivation of adult neural stem cells during Alzheimer's disease.