TY - JOUR T1 - Neuronal network excitability in Alzheimer’s disease: The puzzle of similar versus divergent roles of amyloid β and tau JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0418-20.2020 SP - ENEURO.0418-20.2020 AU - Syed Faraz Kazim AU - Joon Ho Seo AU - Riccardo Bianchi AU - Chloe S. Larson AU - Abhijeet Sharma AU - Robert K.S. Wong AU - Kirill Y. Gorbachev AU - Ana C. Pereira Y1 - 2021/03/18 UR - http://www.eneuro.org/content/early/2021/03/18/ENEURO.0418-20.2020.abstract N2 - Alzheimer’s disease (AD) is the most frequent neurodegenerative disorder that commonly causes dementia in the elderly. Recent evidence indicate 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 Aβ and Tau in the induction of network hyperexcitability. Many patients harboring genetic mutations that lead to increased Aβ production suffer from seizures and epilepsy prior to the development of plaques. Similarly, pathological accumulation of hyperphosphorylated tau has been associated with hyperexcitability in the hippocampus. We present common and divergent roles of tau and Aβ on neuronal hyperexcitability in AD, and hypotheses that could serve as a template for future experiments.Significance statementAbnormal neuronal network excitability may lead to hypersynchrony, aberrant oscillatory rhythmic activity and interneuron dysfunction, which may contribute to cognitive decline in Alzheimer’s disease. The main goals of this review are: (1) to provide an overview of the current knowledge on the association between abnormal network dysfunction and Alzheimer’s disease; (2) discuss the role of pathological Aβ and tau on neuronal hyperexcitability; and (3) present potential hypotheses that can be tested for future studies, which could lead to more effective strategies to prevent, diagnose and manage AD and related disorders. ER -