Impairment of hippocampal long-term potentiation by Alzheimer amyloid ?-peptides
- 16 March 2000
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
Abstract
Although it is generally believed that amyloid β (Aβ) peptides contribute to the pathogenesis of Alzheimer's disease, the precise role of these peptides in the development of memory loss of Alzheimer's disease, has not been fully understood. The present study examined the effect of several synthetic Aβ peptides on long‐term potentiation (LTP), a cellular model of learning and memory, in rat hippocampal slices. Brief perfusion of slices with low concentrations (200 nM or 1 μM) of Aβ1–42, Aβ1–40 or their active fragment Aβ25‐–35 significantly inhibited LTP induction without affecting the basal synaptic transmission and posttetanic potentiation in the dentate medial perforant path. A similar effect of Aβ25–35 was also observed in the Schaffer colleteral‐CA1 pathway. When comparing actions of several Aβ variants derived from Aβ25–35, the N‐terminal sequence of Aβ25–35 was found necessary for inhibiting LTP. In addition, Aβ variants lacking neurotoxic action and aggregating property were also able to block LTP, suggesting that this effect was neurotoxicity independent. Our findings demonstrated that subneurotoxic concentrations of Aβ peptides could strongly suppress long‐term synaptic plasticity in the hippocampus. Such an effect might underlie the memory deficits seen in Alzheimer's disease before neuronal cell loss. J. Neurosci. Res. 60:65–72, 2000Keywords
This publication has 28 references indexed in Scilit:
- Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic miceNature Neuroscience, 1999
- Alzheimer Amyloid Protein Precursor in the Rat Hippocampus: Transport and Processing through the Perforant PathJournal of Neuroscience, 1998
- Block of LTP in rat hippocampus in vivo by β-amyloid precursor protein fragmentsNeuroReport, 1997
- Ionic effects of the Alzheimer's disease β-amyloid precursor protein and its metabolic fragmentsTrends in Neurosciences, 1997
- Pyramidal Nerve Cell Loss in Alzheimer's DiseaseNeurodegeneration, 1996
- Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic MiceScience, 1996
- Impairment of spatial but not contextual memory in CaMKII mutant mice with a selective loss of hippocampal ltp in the range of the θ frequencyCell, 1995
- The Ca2+ influx induced by β‐amyloid peptide 25–35 in cultured hippocampal neurons results from network excitationJournal of Neurobiology, 1995
- Hydrogen peroxide mediates amyloid β protein toxicityCell, 1994
- Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.Proceedings of the National Academy of Sciences, 1993