Network excitability dysfunction in Alzheimer's disease: insights from in vitro and in vivo models

Recent reports have drawn attention to dysfunctions of intrinsic neuronal excitability and network activity in Alzheimer disease (AD). Here we review the possible causes of these basic dysfunctions and implications for AD, based on in vitro and in vivo findings. We then review the current therapeutic approaches particularly linked to the issue of neuronal excitability in AD.

AD is a complex, neurodegenerative disorder. Hippocampal synaptic dysfunction is an early feature of the degenerative process that is clearly linked to memory impairment, the first and major symptom of AD. A growing body of evidence points toward a dysfunction of neuronal networks. Intrinsic neuronal excitability, mainly through profound dysregulation of calcium homeostasis, appears to be largely affected. Consequently, neuronal communication is disturbed. Such cellular defects might underlie cognitive manifestations like fluctuations in cognitive impairment and might also explain several observations obtained with EEG, MEG, MRI, or PET studies, leading to the concept of a disconnection syndrome in AD.