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Review, Disorders of the Nervous System

Neuronal network excitability in Alzheimer’s disease: The puzzle of similar versus divergent roles of amyloid β and tau

Syed Faraz Kazim, Joon Ho Seo, Riccardo Bianchi, Chloe S. Larson, Abhijeet Sharma, Robert K.S. Wong, Kirill Y. Gorbachev and Ana C. Pereira
eNeuro 19 March 2021, ENEURO.0418-20.2020; DOI: https://doi.org/10.1523/ENEURO.0418-20.2020
Syed Faraz Kazim
aDepartment of Neurology & Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
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Joon Ho Seo
aDepartment of Neurology & Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
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Riccardo Bianchi
bThe Robert F. Furchgott Center for Neural and Behavioral Science, and Department of Physiology and Pharmacology, State University of New York (SUNY) Downstate Medical Center, Brooklyn, NY 11203, USA.
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Chloe S. Larson
aDepartment of Neurology & Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
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Abhijeet Sharma
aDepartment of Neurology & Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
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Robert K.S. Wong
bThe Robert F. Furchgott Center for Neural and Behavioral Science, and Department of Physiology and Pharmacology, State University of New York (SUNY) Downstate Medical Center, Brooklyn, NY 11203, USA.
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Kirill Y. Gorbachev
aDepartment of Neurology & Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
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Ana C. Pereira
aDepartment of Neurology & Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
cRonald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
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Abstract

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 statement

Abnormal 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.

  • Amyloid Beta
  • neuronal excitability
  • seizures
  • Tau

Footnotes

  • The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

  • Funding sources: NIH R01AG064020, NIH R01AG063819 and Emerging Leaders Career Development Award in Aging K76AG054772.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Neuronal network excitability in Alzheimer’s disease: The puzzle of similar versus divergent roles of amyloid β and tau
Syed Faraz Kazim, Joon Ho Seo, Riccardo Bianchi, Chloe S. Larson, Abhijeet Sharma, Robert K.S. Wong, Kirill Y. Gorbachev, Ana C. Pereira
eNeuro 19 March 2021, ENEURO.0418-20.2020; DOI: 10.1523/ENEURO.0418-20.2020

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Neuronal network excitability in Alzheimer’s disease: The puzzle of similar versus divergent roles of amyloid β and tau
Syed Faraz Kazim, Joon Ho Seo, Riccardo Bianchi, Chloe S. Larson, Abhijeet Sharma, Robert K.S. Wong, Kirill Y. Gorbachev, Ana C. Pereira
eNeuro 19 March 2021, ENEURO.0418-20.2020; DOI: 10.1523/ENEURO.0418-20.2020
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Keywords

  • Amyloid Beta
  • neuronal excitability
  • seizures
  • Tau

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