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Picomolar Amyloid-β Positively Modulates Synaptic Plasticity and Memory in Hippocampus
Open accessAbstract
Amyloid-β (Aβ) peptides are produced in high amounts during Alzheimer's disease, causing synaptic and memory dysfunction. However, they are also released in lower amounts in normal brains throughout life during synaptic activity. Here we show that low picomolar concentrations of a preparation containing both Aβ 42 monomers and oligomers cause a marked increase of hippocampal long-term potentiation, whereas high nanomolar concentrations lead to the well established reduction of potentiation. Picomolar levels of Aβ 42 also produce a pronounced enhancement of both reference and contextual fear memory. The mechanism of action of picomolar Aβ 42 on both synaptic plasticity and memory involves α7-containing nicotinic acetylcholine receptors. These findings strongly support a model for Aβ effects in which low concentrations play a novel positive, modulatory role on neurotransmission and memory, whereas high concentrations play the well known detrimental effect culminating in dementia.
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“studies that shed light on the physiological role of Aβ in non-diseased brains show that Aβ plays a role in synaptic transmission and is involved in learning and memory formation [18–22].”
From Amyloid-β interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure (2018) · cites this paper as [22]
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“picomolar concentrations of Aβ are sufficient to stimulate nicotinic receptors and subsequently LTP and learning and memory in healthy rodents (Puzzo et al., 2008, 2012; Morley et al., 2010)”
From Emerging Alternative Proteinases in APP Metabolism and Alzheimer’s Disease Pathogenesis: A Focus on MT1-MMP and MT5-MMP (2019) · cites this paper as Puzzo et al., 2008
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“To address this concern, other studies injected picomolar concentrations of Aβ peptides into the mice, which also significantly enhanced synaptic plasticity and memory formation.394”
From Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future (2023) · cites this paper as [394]
In the citing paper
“Remarkably, at sub-nanomolar doses, the effect on LTP is reversed, and Aβ markedly enhances LTP. Discovered by Arancio and colleagues in a detailed analysis (Puzzo et al., 2008), enhancement occurs over a narrow range of concentrations and is associated with presynaptic activation of alpha7 nicotinic receptors.”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Puzzo et al., 2008
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“and synaptic transmission (Puzzo et al., 2008, 2011)”
From Emerging Alternative Proteinases in APP Metabolism and Alzheimer’s Disease Pathogenesis: A Focus on MT1-MMP and MT5-MMP (2019) · cites this paper as Puzzo et al., 2008
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Metadata
- Authors
- Puzzo, D., Privitera, L., Leznik, E., Fà, M., Staniszewski, A., Palmeri, A., & Arancio, O.
- Affiliations
- Columbia University Irving Medical Center (US)
- University of Catania (IT)
- Columbia University (US)
- Corresponding author
- Arancio, Ottavio
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-12-31
- Volume
- 28
- Issue
- 53
- Pages
- 14537-14545
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2673049
- OpenAlex
- W2078917784
- Cited by
- 740
- References
- 56
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 41 · 2023: 38 · 2022: 40 · 2021: 45 · 2020: 49 · 2019: 44 · 2018: 38 · 2017: 46 · 2016: 46 · 2015: 50 · 2014: 51 · 2013: 42 · 2012: 44
- FWCI
- 28.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- Funders
- Alzheimer's Association (NIRG-07-59597)
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS040045, R01NS049442, NS049442)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- amyloid-beta, synaptic plasticity, long-term potentiation, hippocampus, memory, fear memory, contextual fear, alpha7 nicotinic acetylcholine receptor, Alzheimer's disease, amyloid-beta oligomers, neurotransmission
- MeSH terms
- Analysis of Variance, Animals, Bungarotoxins, Dose-Response Relationship, Drug, Electric Stimulation, Hippocampus, Humans, Male, Mecamylamine, Memory, Mice, Inbred C57BL, Neuronal Plasticity, Peptide Fragments, Receptors, Nicotinic, Synapses, 2-Amino-5-phosphonovalerate, Amyloid beta-Peptides, Mice, Knockout, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists, Nicotinic Antagonists, Maze Learning, Excitatory Postsynaptic Potentials, Mice, alpha7 Nicotinic Acetylcholine Receptor, In Vitro Techniques
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