The storm before the quiet: neuronal hyperactivity and aβ in the presymptomatic stages of Alzheimer’s disease
Abstract
Neuronal activity directly promotes the production and secretion of amyloid β (Aβ). Interestingly, neuronal hyperactivity can be observed in presymptomatic stages of both sporadic and familial Alzheimer's disease (AD) and in several AD mouse models. In this review, we will highlight the recent evidence for neuronal hyperactivity before or during the onset of cognitive defects in mild cognitive impairment. Furthermore, we review specific molecular mechanisms through which neuronal hyperactivity affects Aβ production and degradation. With these data, we will provide more insight into the 2-faced nature of neuronal hyperactivity: does enhanced neuronal activity during the presymptomatic stages of AD provide protection against the earliest disease processes or is it a pathogenic contributor to AD?
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Pathological accumulation of Aβ enhances seizure susceptibility and network hyperexcitability by blocking glial uptake of glutamate while enhancing neuronal firing, glutamate release, extrasynaptic NMDA receptor activity, and intracellular Ca2+ concentration.
“Pathological accumulation of Aβ also enhances seizure susceptibility and network hyperexcitability by blocking glial uptake of glutamate while enhancing neuronal firing, glutamate release, extrasynaptic NMDA receptor activity, and intracellular Ca2+ concentration (Stargardt et al., 2015).”
From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as Stargardt et al., 2015
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- Authors
- Stargardt, A., Swaab, D. F., & Bossers, K.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Netherlands Institute for Neuroscience (NL)
- Corresponding author
- Bossers, Koen
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 36
- Issue
- 1
- Pages
- 1-11
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2001731317
- Cited by
- 109
- References
- 19
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 9 · 2023: 8 · 2022: 12 · 2021: 12 · 2020: 11 · 2019: 11 · 2018: 7 · 2017: 8 · 2016: 6 · 2015: 8
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Funders
- Internationale Stichting Alzheimer Onderzoek (11552)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- neuronal hyperactivity, amyloid-beta, preclinical Alzheimer's disease, mild cognitive impairment, amyloid-beta production, amyloid beta degradation, familial Alzheimer's disease, sporadic Alzheimer's disease, mouse models of Alzheimer's disease, neuroprotection
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Humans, Neurons, Amyloid beta-Peptides, Disease Progression, Mice, Proteolysis, Cognitive Dysfunction
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