Cited by 146Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

Alzheimer's disease amyloid β-protein and synaptic function

Ondrejcak, Tomas, Klyubin, Igor, Hu, Neng-Wei, Barry, Andrew E., Cullen, William K., Rowan, Michael J.·2010·NeuroMolecular Medicine

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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Crossref · 10.1007/s12017-009-8091-0

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186 of 186 references verified0 citation errors · 0 not checkable

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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
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

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