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PMID: 19304802 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Synaptic transmission block by presynaptic injection of oligomeric amyloid beta.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 106 ·No. 14 ·2009-04-07 ·Pages 5901-6

Moreno H, Yu E, Pigino G, Hernandez AI, Kim N, Moreira JE, Sugimori M, Llinás RR

Abstract

Early Alzheimer's disease (AD) pathophysiology is characterized by synaptic changes induced by degradation products of amyloid precursor protein (APP). The exact mechanisms of such modulation are unknown. Here, we report that nanomolar concentrations of intraaxonal oligomeric (o)Abeta42, but not oAbeta40 or extracellular oAbeta42, acutely inhibited synaptic transmission at the squid giant synapse. Further characterization of this phenotype demonstrated that presynaptic calcium currents were unaffected. However, electron microscopy experiments revealed diminished docked synaptic vesicles in oAbeta42-microinjected terminals, without affecting clathrin-coated vesicles. The molecular events of this modulation involved casein kinase 2 and the synaptic vesicle rapid endocytosis pathway. These findings open the possibility of a new therapeutic target aimed at ameliorating synaptic dysfunction in AD.

MeSH Terms
Amyloid beta-Peptides/administration & dosage,pharmacology Animals Casein Kinase II Decapodiformes Electrophysiology Endocytosis Microscopy, Electron Peptide Fragments Presynaptic Terminals Synaptic Transmission/drug effects
Chemicals
Amyloid beta-Peptides Peptide Fragments amyloid beta-protein (1-40) amyloid beta-protein (1-42) Casein Kinase II
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Moreno Herman
Department of Neurology and Physiology/Pharmacology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
Yu Eunah
Pigino Gustavo
Hernandez Alejandro I
Kim Natalia
Moreira Jorge E
Sugimori Mutsuyuki
Llinás Rodolfo R
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0900944106
Published
2009-04-07
Epub
2009-00-20
Pages
5901-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2659170
Subset
IM
Grants
NIA NIH HHS · K08 AG027476 · United States
NINDS NIH HHS · P01 NS013742 · United States
NIA NIH HHS · AG027476 · United States
NINDS NIH HHS · NS13742-30 · United States
External Links
PubMed source DOI: 10.1073/pnas.0900944106 PMC Full Text View journal details
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