Cited by 499Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

Amyloid-β as a positive endogenous regulator of release probability at hippocampal synapses

Abramov, Efrat, Dolev, Iftach, Fogel, Hilla, Ciccotosto, Giuseppe D, Ruff, Eyal, Slutsky, Inna·2009·Nature Neuroscience

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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Crossref · 10.1038/nn.2433

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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
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

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