Amyloid-β as a positive endogenous regulator of release probability at hippocampal synapses
Abstract
Accumulation of cerebral amyloid-beta peptide (Abeta) is essential for developing synaptic and cognitive deficits in Alzheimer's disease. However, the physiological functions of Abeta, as well as the primary mechanisms that initiate early Abeta-mediated synaptic dysfunctions, remain largely unknown. Here we examine the acute effects of endogenously released Abeta peptides on synaptic transfer at single presynaptic terminals and synaptic connections in rodent hippocampal cultures and slices. Increasing extracellular Abeta by inhibiting its degradation enhanced release probability, boosting ongoing activity in the hippocampal network. Presynaptic enhancement mediated by Abeta was found to depend on the history of synaptic activation, with lower impact at higher firing rates. Notably, both elevation and reduction in Abeta levels attenuated short-term synaptic facilitation during bursts in excitatory synaptic connections. These observations suggest that endogenous Abeta peptides have a crucial role in activity-dependent regulation of synaptic vesicle release and might point to the primary pathological events that lead to compensatory synapse loss in Alzheimer's disease.
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Aβ monomers can trigger or sustain intracellular signaling essential for synaptic plasticity and homeostasis.
“Aβ monomers can trigger or sustain intracellular signaling essential for synaptic plasticity and homeostasis (101–103).”
From The β-Secretase BACE1 in Alzheimer’s Disease (2021) · cites this paper as [101]
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- Authors
- Abramov, E., Dolev, I., Fogel, H., Ciccotosto, G. D., Ruff, E., & Slutsky, I.
- Affiliations
- Tel Aviv University (IL)
- Mental Health Research Institute (AU)
- Corresponding author
- Slutsky, Inna
- Venue
- Nature Neuroscience
- Published
- 2009-11-22
- Volume
- 12
- Issue
- 12
- Pages
- 1567-1576
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2109221379
- Cited by
- 499
- References
- 50
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 20 · 2023: 26 · 2022: 21 · 2021: 43 · 2020: 32 · 2019: 43 · 2018: 31 · 2017: 34 · 2016: 41 · 2015: 26 · 2014: 34 · 2013: 30 · 2012: 36
- FWCI
- 19.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta, release probability, synaptic transmission, hippocampus, short-term plasticity, synaptic facilitation, presynaptic terminals, synaptic vesicle release, activity-dependent regulation, Alzheimer's disease, excitatory synapses, synaptic loss
- MeSH terms
- Alzheimer Disease, Animals, Membrane Potentials, Neural Inhibition, Synaptic Transmission, Neuronal Plasticity, Organ Culture Techniques, Protease Inhibitors, Synaptic Vesicles, Tetrodotoxin, Thiorphan, Neprilysin, Amyloid beta-Peptides, Presynaptic Terminals, Excitatory Postsynaptic Potentials, Sodium Channel Blockers, Rats, CA1 Region, Hippocampal
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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