One of the most important symptoms of Alzheimer's disease is a dramatic reduction in episodic memory, a task dependent on the hippocampus. These symptoms occur usually later in life but the underlying neuronal changes probably developed over decades. There is now more emphasis in the Alzheimer's disease field to find very early biomarkers of the disease so that an effective pharmacological approach may be used to prevent the occurrence of disease or slow down the disease process. There has been suggestion that early alterations of hippocampal networks might lead to perturbations of hippocampal oscillatory activity which are essential for episodic memory. Brain oscillations in the theta (3-12Hz) and gamma frequency bands (30-250Hz) are crucial for supporting normal cognitive and executive functioning. Moreover, it was recently found that the magnitude of the coupling between these two oscillations (or coupling strength) was positively associated with memory in humans and in rats. Therefore, hippocampal oscillations might be altered in the early stage of AD. In this presentation, I will show evidence in a mouse model of AD (CRND8 mice), that high-gamma frequency band (200Hz) becomes uncoupled to theta frequency oscillations in the subiculum, the main output region of the hippocampus. I will show some of the physiological consequences of this uncoupling and suggest how alterations of GABAergic interneurons may be responsible in this process. The results provide indications that theta-gamma uncoupling may be an early biomarker in AD.