Excitatory-inhibitory imbalance in Alzheimer's disease and therapeutic significance

Abstract

The interplay between excitatory and inhibitory circuits underlies the brain's processes and their dysregulation has been linked to cognitive decline, psychiatric disorders and epilepsy. In patients with Alzheimer's disease (AD), an elevated occurrence of seizures has been observed in both sporadic and familial forms of the condition. Although seizure activity in AD has been mainly viewed as a result of neuronal cell loss and considered to occur in later stages, it is now becoming increasingly clear that aberrant neuronal activity may be more common in patients at earlier stages than previously thought and may trigger and contribute significantly to cognitive defects. Here, we review alterations of inhibitory and excitatory circuits that may lead to overexcitability and early dysregulation of neuronal networks in the context of AD and therapeutic outcomes of restoring excitatory/inhibitory balance.