Neuronal network excitability in alzheimer’s disease: The puzzle of similar versus divergent roles of amyloid B and TAU

Abstract

Alzheimer’s disease (AD) is the most frequent neurodegenerative disorder that commonly causes dementia in the elderly. Recent evidence indicates that network abnormalities, including hypersynchrony, altered oscillatory rhythmic activity, interneuron dysfunction, and synaptic depression, may be key mediators of cognitive decline in AD. In this review, we discuss characteristics of neuronal network excitability in AD, and the role of Ab and tau in the induction of network hyperexcitability. Many patients harboring genetic mutations that lead to increased Ab production suffer from seizures and epilepsy before the development of plaques. Similarly, pathologic accumulation of hyperphosphorylated tau has been associated with hyperexcitability in the hippocampus. We present common and divergent roles of tau and Ab on neuronal hyperexcitability in AD, and hypotheses that could serve as a template for future experiments.