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Impairment of hippocampal long‐term potentiation by Alzheimer amyloid β‐peptides
Author(s) -
Chen QiSheng,
Kagan Bruce L.,
Hirakura Yutaka,
Xie CuiWei
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(20000401)60:1<65::aid-jnr7>3.0.co;2-q
Subject(s) - long term potentiation , hippocampal formation , neuroscience , schaffer collateral , perforant path , synaptic plasticity , hippocampus , neurotoxicity , chemistry , alzheimer's disease , biology , medicine , biochemistry , dentate gyrus , disease , receptor , organic chemistry , toxicity
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 Aβ 1–42 , Aβ 1–40 or their active fragment Aβ 25‐–35 significantly inhibited LTP induction without affecting the basal synaptic transmission and posttetanic potentiation in the dentate medial perforant path. A similar effect of Aβ 25–35 was also observed in the Schaffer colleteral‐CA1 pathway. When comparing actions of several Aβ variants derived from Aβ 25–35 , the N ‐terminal sequence of Aβ 25–35 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, 2000 © 2000 Wiley‐Liss, Inc.