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Extracellular Forms of Aβ and Tau from iPSC Models of Alzheimer’s Disease Disrupt Synaptic Plasticity
The early stages of Alzheimer’s disease are associated with synaptic dysfunction prior to overt loss of neurons. To identify extracellular molecules that impair synaptic plasticity in the brain, we studied the secretomes of human iPSC-derived neuronal models of Alzheimer’s disease. When introduced i...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972225/ https://www.ncbi.nlm.nih.gov/pubmed/29768194 http://dx.doi.org/10.1016/j.celrep.2018.04.040 |
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author | Hu, Neng-Wei Corbett, Grant T. Moore, Steven Klyubin, Igor O’Malley, Tiernan T. Walsh, Dominic M. Livesey, Frederick J. Rowan, Michael J. |
author_facet | Hu, Neng-Wei Corbett, Grant T. Moore, Steven Klyubin, Igor O’Malley, Tiernan T. Walsh, Dominic M. Livesey, Frederick J. Rowan, Michael J. |
author_sort | Hu, Neng-Wei |
collection | PubMed |
description | The early stages of Alzheimer’s disease are associated with synaptic dysfunction prior to overt loss of neurons. To identify extracellular molecules that impair synaptic plasticity in the brain, we studied the secretomes of human iPSC-derived neuronal models of Alzheimer’s disease. When introduced into the rat brain, secretomes from human neurons with either a presenilin-1 mutation, amyloid precursor protein duplication, or trisomy of chromosome 21 all strongly inhibit hippocampal long-term potentiation. Synaptic dysfunction caused by presenilin-1 mutant and amyloid precusor protein duplication secretomes is mediated by Aβ peptides, whereas trisomy of chromosome 21 (trisomy 21) neuronal secretomes induce dysfunction through extracellular tau. In all cases, synaptotoxicity is relieved by antibody blockade of cellular prion protein. These data indicate that human models of Alzheimer’s disease generate distinct proteins that converge at the level of cellular prion protein to induce synaptic dysfunction in vivo. |
format | Online Article Text |
id | pubmed-5972225 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-59722252018-06-01 Extracellular Forms of Aβ and Tau from iPSC Models of Alzheimer’s Disease Disrupt Synaptic Plasticity Hu, Neng-Wei Corbett, Grant T. Moore, Steven Klyubin, Igor O’Malley, Tiernan T. Walsh, Dominic M. Livesey, Frederick J. Rowan, Michael J. Cell Rep Article The early stages of Alzheimer’s disease are associated with synaptic dysfunction prior to overt loss of neurons. To identify extracellular molecules that impair synaptic plasticity in the brain, we studied the secretomes of human iPSC-derived neuronal models of Alzheimer’s disease. When introduced into the rat brain, secretomes from human neurons with either a presenilin-1 mutation, amyloid precursor protein duplication, or trisomy of chromosome 21 all strongly inhibit hippocampal long-term potentiation. Synaptic dysfunction caused by presenilin-1 mutant and amyloid precusor protein duplication secretomes is mediated by Aβ peptides, whereas trisomy of chromosome 21 (trisomy 21) neuronal secretomes induce dysfunction through extracellular tau. In all cases, synaptotoxicity is relieved by antibody blockade of cellular prion protein. These data indicate that human models of Alzheimer’s disease generate distinct proteins that converge at the level of cellular prion protein to induce synaptic dysfunction in vivo. Cell Press 2018-05-15 /pmc/articles/PMC5972225/ /pubmed/29768194 http://dx.doi.org/10.1016/j.celrep.2018.04.040 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hu, Neng-Wei Corbett, Grant T. Moore, Steven Klyubin, Igor O’Malley, Tiernan T. Walsh, Dominic M. Livesey, Frederick J. Rowan, Michael J. Extracellular Forms of Aβ and Tau from iPSC Models of Alzheimer’s Disease Disrupt Synaptic Plasticity |
title | Extracellular Forms of Aβ and Tau from iPSC Models of Alzheimer’s Disease Disrupt Synaptic Plasticity |
title_full | Extracellular Forms of Aβ and Tau from iPSC Models of Alzheimer’s Disease Disrupt Synaptic Plasticity |
title_fullStr | Extracellular Forms of Aβ and Tau from iPSC Models of Alzheimer’s Disease Disrupt Synaptic Plasticity |
title_full_unstemmed | Extracellular Forms of Aβ and Tau from iPSC Models of Alzheimer’s Disease Disrupt Synaptic Plasticity |
title_short | Extracellular Forms of Aβ and Tau from iPSC Models of Alzheimer’s Disease Disrupt Synaptic Plasticity |
title_sort | extracellular forms of aβ and tau from ipsc models of alzheimer’s disease disrupt synaptic plasticity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972225/ https://www.ncbi.nlm.nih.gov/pubmed/29768194 http://dx.doi.org/10.1016/j.celrep.2018.04.040 |
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