Alzheimer's disease amyloid β-protein and synaptic function
Abstract
Alzheimer's disease (AD) is characterized neuropathologically by the deposition of different forms of amyloid beta-protein (A beta) including variable amounts of soluble species that correlate with severity of dementia. The extent of synaptic loss in the brain provides the best morphological correlate of cognitive impairment in clinical AD. Animal research on the pathophysiology of AD has therefore focussed on how soluble A beta disrupts synaptic mechanisms in vulnerable brain regions such as the hippocampus. Synaptic plasticity in the form of persistent activity-dependent increases or decreases in synaptic strength provide a neurophysiological substrate for hippocampal-dependent learning and memory. Acute treatment with human-derived or chemically prepared soluble A beta that contains certain oligomeric assemblies, potently and selectively disrupts synaptic plasticity causing inhibition of long-term potentiation (LTP) and enhancement of long-term depression (LTD) of glutamatergic transmission. Over time these and related actions of A beta have been implicated in reducing synaptic integrity. This review addresses the involvement of neurotransmitter intercellular signaling in mediating or modulating the synaptic plasticity disrupting actions of soluble A beta, with particular emphasis on the different roles of glutamatergic and cholinergic mechanisms. There is growing evidence to support the view that NMDA and possibly nicotinic receptors are critically involved in mediating t…
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Aβ inhibits long-term potentiation (LTP) in the hippocampus.
“Previous reports consistently show that Aβ inhibits long-term potentiation (LTP) in the hippocampus (Ondrejcak et al., 2010), a widely accepted cellular model for learning and memory (Bliss and Collingridge, 1993)”
From Wild-Type, but Not Mutant N296H, Human Tau Restores Aβ-Mediated Inhibition of LTP in Tau−/− mice (2017) · cites this paper as Ondrejcak et al., 2010
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RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
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- Authors
- Ondrejcak, T., Klyubin, I., Hu, N.-W., Barry, A. E., Cullen, W. K., & Rowan, M. J.
- Affiliations
- Trinity College Dublin (IE)
- Corresponding author
- Rowan, Michael J.
- Venue
- NeuroMolecular Medicine
- Published
- 2009-09-16
- Volume
- 12
- Issue
- 1
- Pages
- 13-26
- ISSN
- 1535-1084 (ISSN-L)
- 1559-1174
- OpenAlex
- W2150302044
- Cited by
- 146
- References
- 189
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 7 · 2023: 2 · 2022: 7 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 16 · 2016: 5 · 2015: 7 · 2014: 10 · 2013: 13 · 2012: 18
- FWCI
- 10.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- NeuroMolecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Health Research Board
- Science Foundation Ireland
- 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
- Alzheimer's disease, amyloid-beta, soluble amyloid-beta oligomers, synaptic plasticity, long-term potentiation, long-term depression, glutamatergic neurotransmission, cholinergic mechanisms, NMDA receptor, nicotinic acetylcholine receptors, muscarinic receptors, hippocampus, synaptic loss, neurotransmitter signaling
- MeSH terms
- Acetylcholine, Alzheimer Disease, Animals, Humans, Synaptic Transmission, Receptors, Cholinergic, Synapses, Receptors, N-Methyl-D-Aspartate, Amyloid beta-Peptides, Long-Term Potentiation, Glutamic Acid, Long-Term Synaptic Depression
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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