Neuroglial cells are fundamental for brain homeostasis and they represent the intrinsic brain defence system. Therefore, all forms of neuropathological processes inevitably involve glial cells. Neurodegenerative diseases, including Alzheimer's disease (AD) disrupt brain connectivity affecting neuronal-neuronal, neuronal-glial and glial-glial contacts and interaction. In addition neurodegenerative processes trigger universal and conserved glial reactions represented by astrogliosis and microglial activation. The complex of recently acquired knowledge allows us to regard the neurodegenerative diseases as primarily gliodegenerative processes, in which glial cells determine the progression and outcome of neuropathological processes such as AD. We have recently probed this active pathological role, by showing: (i) an astroglial generalised atrophy with a concomitant astrogliosis just restricted to Ab plaques presence ii) alterations in glutamate glial metabolism and (iii) an early resting microglial recruitment in the affected areas, even before the presence of activated/macrophagic microglial cells. These glial alterations are fundamental for the disruption of neural networks connectivity as well as with the neurotransmitters imbalance that underlie the mnesic deficits associated with AD.