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

Hai Wei Wang, Joseph F. Pasternak, Helen Kuo, Helen Ristic, Mary P. Lambert, Brett Chromy, Kirsten L. Viola, William L. Klein, W. Blaine Stine, Grant A. Krafft, Barbara L. Trommer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

498 Scopus citations


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 (Aβ) in fibrillar form. Recently it has been demonstrated that non-fibrillar assemblies of Aβ 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 Aβ1-42 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 Aβ-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.

Original languageEnglish (US)
Pages (from-to)133-140
Number of pages8
JournalBrain research
Issue number2
StatePublished - Jan 11 2002


  • Aβ-derived diffusible ligand
  • Dentate gyrus
  • Long-term depression
  • Long-term potentiation
  • Neuroplasticity

ASJC Scopus subject areas

  • Clinical Neurology
  • Molecular Biology
  • General Neuroscience
  • Developmental Biology


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