Cited by 527Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

Soluble oligomers of β amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus

Wang, Hai-Wei, Pasternak, Joseph F, Kuo, Helen, Ristic, Helen, Lambert, Mary P, Chromy, Brett, Viola, Kirsten L, Klein, William L +3 more·2002·Brain Research

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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Crossref · 10.1016/s0006-8993(01)03058-x

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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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