The effect of amyloid-β peptide on synaptic plasticity and memory is influenced by different isoforms, concentrations, and aggregation status

NEUROBIOLOGY OF AGING

卷:71

Article

Gulisano, Walter¹  Melone, Marcello^2,3  Li Puma, Domenica D.⁴  Tropea, Maria Rosaria¹  Palmeri, Agostino¹  Arancio, Ottavio⁵  Grassi, Claudio^4,6  Conti, Fiorenzo^2,3,7  Puzzo, Daniela¹ 

[1] Univ Catania, Dept Biomed & Biotechnol Sci, Catania, Italy

[2] Univ Politecn Marche, Dept Expt & Clin Med, Sect Neurosci & Cell Biol, Ancona, Italy

[3] IRCCS, INRCA, Ctr Neurobiol Aging, Ancona, Italy

[4] Univ Cattolica, Med Sch, Inst Human Physiol, Rome, Italy

[5] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA

[6] Fdn Policlin Univ A Gemelli, Rome, Italy

[7] Univ Politecn Marche, Fdn Mol Med, Ancona, Italy

关键词: Beta amyloid;    Oligomers;    Monomers;    Long-term potentiation;    Memory;    Hippocampus;   

DOI  :  10.1016/j.neurobiolaging.2018.06.025

来源: Elsevier

【 摘 要 】

The increase of oligomeric amyloid-beta (oA beta) has been related to synaptic dysfunction, thought to be the earliest event in Alzheimer's disease pathophysiology. Conversely, the suppression of endogenous A beta impaired synaptic plasticity and memory, suggesting that the peptide is needed in the healthy brain. However, different species, aggregation forms and concentrations of A beta might differently influence synaptic function/dysfunction. Here, we have tested the contribution of monomeric and oligomeric A beta 42 and A beta 40 at 200 nM and 200 pM concentrations on hippocampal long-term potentiation and spatial memory. We found that, when at 200 nM, oA beta 40, oA beta 42, and monomeric A beta 42 impaired long-term potentiation and memory, whereas only oA beta 42 200 pM enhanced synaptic plasticity and memory and rescued the detrimental effect due to depletion of endogenous A beta. Interestingly, quantification of monomer-like and oligomer-like species carried out by transmission electron microscopy revealed an increase of the monomer/oligomer ratio in the oA beta 42 200 pM preparation, suggesting that the content of monomers and oligomers depends on the final concentration of the solution. (C) 2018 Elsevier Inc. All rights reserved.

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