Endogenous amyloid-β is necessary for hippocampal synaptic plasticity and memory

Authors

  • Daniela Puzzo MD, PhD,

    1. Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY
    2. Department of Physiological Sciences, University of Catania, Catania, Italy
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  • Lucia Privitera PhD,

    1. Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY
    2. Department of Physiological Sciences, University of Catania, Catania, Italy
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  • Mauro Fa' PhD,

    1. Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY
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  • Agnieszka Staniszewski PhD,

    1. Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY
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  • Gakuji Hashimoto PhD,

    1. Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY
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  • Fahad Aziz MD,

    1. Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY
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  • Mikako Sakurai PhD,

    1. Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY
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  • Elena M. Ribe PhD,

    1. Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY
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  • Carol M. Troy MD, PhD,

    1. Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY
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  • Marc Mercken PhD,

    1. Janssen Pharmaceutica, Johnson & Johnson Pharmaceutical Research & Development, Beerse, Belgium
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  • Sonia S. Jung PhD,

    1. Centocor R&D, Inc., Radnor, PA
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  • Agostino Palmeri MD, PhD,

    1. Department of Physiological Sciences, University of Catania, Catania, Italy
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  • Ottavio Arancio MD, PhD

    Corresponding author
    1. Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY
    • Department of Pathology and theTaubInstitute for Research on Alzheimer's Disease and the Aging Brain, P&S #12-420D, 630W 168th St., New York, NY 10032
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Abstract

Objective:

The goal of this study was to investigate the role of endogenous amyloid-β peptide (Aβ) in healthy brain.

Methods:

Long-term potentiation (LTP), a type of synaptic plasticity that is thought to be associated with learning and memory, was examined through extracellular field recordings from the CA1 region of hippocampal slices, whereas behavioral techniques were used to assess contextual fear memory and reference memory. Amyloid precursor protein (APP) expression was reduced through small interfering RNA (siRNA) technique.

Results:

We found that both antirodent Aβ antibody and siRNA against murine APP reduced LTP as well as contextual fear memory and reference memory. These effects were rescued by the addition of human Aβ42, suggesting that endogenously produced Aβ is needed for normal LTP and memory. Furthermore, the effect of endogenous Aβ on plasticity and memory was likely due to regulation of transmitter release, activation of α7-containing nicotinic acetylcholine receptors, and Aβ42 production.

Interpretation:

Endogenous Aβ42 is a critical player in synaptic plasticity and memory within the normal central nervous system. This needs to be taken into consideration when designing therapies aiming at reducing Aβ levels to treat Alzheimer disease. Ann Neurol 2011;

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