Soluble oligomers of β amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus
Abstract
The dementia in Alzheimer disease (AD) is usually attributed to widespread neuronal loss in conjunction with the pathologic hallmarks of intracellular neurofibrillary tangles and extracellular plaques containing amyloid (A beta) in fibrillar form. Recently it has been demonstrated that non-fibrillar assemblies of A beta possess electrophysiologic activity, with the corollary that they may produce dementia by disrupting neuronal signaling prior to cell death. We therefore examined the effects of soluble oligomers of A beta(1-42) on long-term potentiation (LTP) and long-term depression (LTD), two cellular models of memory, in the dentate gyrus of rat hippocampal slices. Compared with vehicle controls, slices pre-incubated 60 min in the presence of A beta-derived diffusible ligands (ADDLs) showed no differences in threshold intensity to evoke a synaptic response, slope of field excitatory post-synaptic potentials (EPSPs), or the input/output function. Tetanus-induced LTP and reversal of LTD were strongly inhibited in ADDLs-treated slices whereas LTD was unaffected. These data suggest that soluble non-fibrillar amyloid may contribute to the pathogenesis of AD both by impairing LTP/memory formation at the cellular level and by creating 'neuroplasticity imbalance' manifested by unopposed LTD in the setting of impaired capacity for neural repair via reversal of LTD or LTP.
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Disruption of functional plasticity by Aβ oligomers includes promotion of LTD, not inhibition.
“Disruption of functional plasticity includes LTD, which is promoted, not inhibited (Shankar et al., 2008; Wang et al., 2002).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Wang et al., 2002
Soluble Aβ oligomers impair synaptic plasticity by inhibiting hippocampal long-term potentiation.
“In vitro and in vivo studies have now indicated that soluble Aβ oligomers impair synaptic plasticity, inhibiting hippocampal long-term potentiation (LTP), the electrophysiological correlate of learning and memory (3 –6).”
From Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein (2010) · cites this paper as [6]
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- Authors
- Wang, H.-W., Pasternak, J. F., Kuo, H., Ristic, H., Lambert, M. P., Chromy, B., Viola, K. L., Klein, W. L., Stine, W. B., Krafft, G. A., & Trommer, B. L.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Trommer, Barbara L
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 924
- Issue
- 2
- Pages
- 133-140
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2004968757
- Cited by
- 527
- References
- 46
- Citations by year
- 2026: 12 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 21 · 2020: 13 · 2019: 14 · 2018: 18 · 2017: 21 · 2016: 19 · 2015: 14 · 2014: 21 · 2013: 26 · 2012: 31
- FWCI
- 14.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1p01ag015501-01)
- National Institute on Aging (AG-15501)
- 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 › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- amyloid-beta 42, soluble oligomers, Alzheimer's disease, long-term potentiation, long-term depression, dentate gyrus, hippocampus, synaptic plasticity, memory formation, tetanic stimulation
- MeSH terms
- Animals, Female, Male, Neural Inhibition, Neuronal Plasticity, Peptide Fragments, Solubility, Synapses, Amyloid beta-Peptides, Rats, Sprague-Dawley, Long-Term Potentiation, Dentate Gyrus, Excitatory Postsynaptic Potentials, Rats
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