About this Research Topic

Background

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. Growing evidence indicates that network abnormalities including hypersynchrony, excitatory/inhibitory imbalance, synaptic depression, and altered oscillatory rhythmic activity might be key determinants of cognitive decline in AD and other related dementias. Importantly, the hyperactivation of the hippocampus, which represents the hub of learning and memory and the most affected brain area in AD, is a consistent fMRI signature in the early phases of the disease. Although the studies reporting molecular evidence about a causal role of neuronal network hyperexcitability in memory impairment are still scarce, compelling reasons argue in favor of this hypothesis:
(i) AD severity was reported to correlate with seizure susceptibility;
(ii) several studies reported the beneficial effect of anti-epileptic drugs on cognition in AD patients and mouse models;
(iii) in Amyloid-β (Aβ)-based AD transgenic mice, neuronal hyperexcitability and epileptiform activity have been observed much before the deposition of Aβ plaques and the appearance of evident cognitive impairment.
By contrast, the data provided thus far on the role of Tau in neuronal network hyperexcitability are controversial, hence whether and how Tau promotes this phenomenon remains currently unclear.

As key determinants of membrane excitability and neurotransmission, diverse ion channels have proven to have a pathogenic role in AD-related neuronal hyperexcitability. Alterations in the biophysical properties and/or expression levels of different ion channels have been found to induce aberrant excitability phenotypes in both Aβ- and Tau-based AD experimental models. However, the link between ion channel alterations and AD onset has been poorly considered.

In this Research Topic, we will address the aforementioned issues, among others, and explore the causal link between ion channel dysfunction, neuronal hyperexcitability, and cognitive impairment in AD and related dementias. The ultimate goal will be a deeper knowledge of those mechanisms and processes that could provide new molecular targets and novel therapeutic avenues.

This Research Topic welcomes the submission of any types of manuscripts supported by the Journal (Original Research, Review, Case Reports, etc.) concerning, but not limited to, the following themes:
- Mechanisms underlying the causal relationship between neuronal excitability and cognitive decline
- Clinical relevance of seizures and epileptiform activity in AD and other related dementias
- Involvement of ion channel dysfunction in the pathogenesis of AD and related dementias
- Mechanisms underlying aberrant network activity and epileptogenesis in AD and related dementias
- Role of Aβ and Tau in neuronal network hyperexcitability
- Involvement of neuroglia and neuroinflammation in the AD-related neuronal network hyperexcitability
- Identification of key genes and molecular genetic mechanisms contributing to hyperexcitability and epilepsy in AD and related dementias
- Correlation between brain energy metabolism and neuronal hyperexcitability in AD and related dementias
- Discussion of new putative therapeutic strategies targeting neuronal hyperexcitability and epileptiform activity in AD and related dementias

Dr. Fiona LeBeau has received funding from Takeda Pharmaceutical Company and Neurexpert. Prof. Anna Pannaccione is a co-author on patent for “7-nitro-5-phenyl-1-(pyrrolidin-1-ylmethyl)-1H-benzo[E][1,4]diazepin-2(3H)-one and other benzodiazepine derivatives" (PCT/EP2011/071252). Dr. Ilaria Piccialli declares no competing interests with regard to the Research Topic subject.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

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• Community Case Study
• Data Report
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• General Commentary
• Hypothesis and Theory
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Community Case Study
• Data Report
• Editorial
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Alzheimer's disease, dementia, neurodegenerative diseases, neuronal hyperexcitability, ion channels, epileptogenesis

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