Neuronal hyperactivity--A key defect in Alzheimer’s disease?
Abstract
Traditionally, the impairment of cognitive functions in Alzheimeŕs disease (AD) is thought to result from a reduction in neuronal and synaptic activities, and ultimately cell death. Here, we review recent in vivo evidence from mouse models and human patients indicating that, particularly in early stages of AD, neuronal circuits are hyperactive instead of hypoactive. Functional analyses at many levels, from single neurons to neuronal populations to large‐scale networks, with a variety of electrophysiological and imaging techniques have revealed two forms of AD‐related hyperactivity and provided first insights into the synaptic mechanisms. The unexpected finding that hyperactivity is an early neuronal dysfunction represents a major conceptual shift in our understanding of AD that may have important implications for the development of therapeutic approaches.
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Amyloid pathology induces abnormal theta and gamma oscillations, likely due to deficient inhibitory interneuron activity.
“Previous studies show that amyloid pathology induces abnormal theta and gamma oscillations, likely due to deficient inhibitory interneuron activity, not examined here20,49,50.”
From The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway (2025) · cites this paper as [49]
Amyloid pathology induces abnormal theta and gamma oscillations, likely due to deficient inhibitory interneuron activity.
“Previous studies have shown that amyloid pathology induces abnormal theta and gamma oscillations, likely due to deficient inhibitory interneuron activity”
From <i>APOE3</i> - <i>R136S</i> mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition (2024) · cites this paper as [47]
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- Authors
- Busche, M. A., & Konnerth, A.
- Affiliations
- Center for Integrated Protein Science Munich (DE)
- Corresponding author
- Konnerth, Arthur
- Venue
- BioEssays
- Publisher
- Wiley
- Published
- 2015-03-14
- Volume
- 37
- Issue
- 6
- Pages
- 624-632
- ISSN
- 0265-9247 (ISSN-L)
- 1521-1878
- OpenAlex
- W2166931244
- Cited by
- 266
- References
- 21
- Citations by year
- 2026: 24 · 2025: 28 · 2024: 29 · 2023: 36 · 2022: 28 · 2021: 32 · 2020: 27 · 2019: 19 · 2018: 12 · 2017: 15 · 2016: 11 · 2015: 5
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- BioEssays (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, neuronal hyperactivity, early Alzheimer's disease, neural circuits, synaptic dysfunction, cognitive impairment, mouse model, electrophysiology, neuroimaging, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Hippocampus, Humans, Synaptic Transmission, Neurons, Feedback, Physiological, Plaque, Amyloid
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