Soluble Aβ Promotes Wild-Type Tau Pathology in vivo
Growing evidence suggests that soluble Aβ species can drive Alzheimer disease (AD) pathogenesis by inducing a cascade of events including tau hyperphosphorylation, proteasome impairment and synaptic dysfunction. However, these studies have relied largely on in vitro approaches to examine the role of...
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ftpubmed:oai:pubmedcentral.nih.gov:3586232 2023-05-15T15:05:42+02:00 Soluble Aβ Promotes Wild-Type Tau Pathology in vivo Chabrier, Meredith A. Blurton-Jones, Mathew Agazaryan, Andranik A. Nerhus, Joy L. Martinez-Coria, Hilda LaFerla, Frank M. 2012-11-28 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586232 http://www.ncbi.nlm.nih.gov/pubmed/23197725 https://doi.org/10.1523/JNEUROSCI.0172-12.2012 en eng http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586232 http://www.ncbi.nlm.nih.gov/pubmed/23197725 http://dx.doi.org/10.1523/JNEUROSCI.0172-12.2012 Article Text 2012 ftpubmed https://doi.org/10.1523/JNEUROSCI.0172-12.2012 2013-09-04T20:33:10Z Growing evidence suggests that soluble Aβ species can drive Alzheimer disease (AD) pathogenesis by inducing a cascade of events including tau hyperphosphorylation, proteasome impairment and synaptic dysfunction. However, these studies have relied largely on in vitro approaches to examine the role of soluble Aβ in AD. In particular, it remains unknown whether soluble Aβ oligomers can facilitate the development of human wild-type tau pathology in vivo. To address this question, we developed a novel transgenic model that expresses low levels of APP with the Arctic familial AD mutation to enhance soluble Aβ oligomer formation in conjunction with wild-type human tau. Using a genetic approach, we show that reduction of β-site APP cleaving enzyme (BACE) in these “ArcTau” mice decreases soluble Aβ oligomers, rescues cognition, and more importantly also reduces tau accumulation and phosphorylation. Notably, BACE reduction decreases the postsynaptic mislocalization of tau in ArcTau mice, and reduces the association between NMDA receptors and PSD-95. These studies provide critical in vivo evidence for a strong mechanistic link between soluble Aβ, wild-type tau and synaptic pathology. Text Arctic PubMed Central (PMC) Arctic Journal of Neuroscience 32 48 17345 17350 |
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Article Chabrier, Meredith A. Blurton-Jones, Mathew Agazaryan, Andranik A. Nerhus, Joy L. Martinez-Coria, Hilda LaFerla, Frank M. Soluble Aβ Promotes Wild-Type Tau Pathology in vivo |
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Growing evidence suggests that soluble Aβ species can drive Alzheimer disease (AD) pathogenesis by inducing a cascade of events including tau hyperphosphorylation, proteasome impairment and synaptic dysfunction. However, these studies have relied largely on in vitro approaches to examine the role of soluble Aβ in AD. In particular, it remains unknown whether soluble Aβ oligomers can facilitate the development of human wild-type tau pathology in vivo. To address this question, we developed a novel transgenic model that expresses low levels of APP with the Arctic familial AD mutation to enhance soluble Aβ oligomer formation in conjunction with wild-type human tau. Using a genetic approach, we show that reduction of β-site APP cleaving enzyme (BACE) in these “ArcTau” mice decreases soluble Aβ oligomers, rescues cognition, and more importantly also reduces tau accumulation and phosphorylation. Notably, BACE reduction decreases the postsynaptic mislocalization of tau in ArcTau mice, and reduces the association between NMDA receptors and PSD-95. These studies provide critical in vivo evidence for a strong mechanistic link between soluble Aβ, wild-type tau and synaptic pathology. |
format |
Text |
author |
Chabrier, Meredith A. Blurton-Jones, Mathew Agazaryan, Andranik A. Nerhus, Joy L. Martinez-Coria, Hilda LaFerla, Frank M. |
author_facet |
Chabrier, Meredith A. Blurton-Jones, Mathew Agazaryan, Andranik A. Nerhus, Joy L. Martinez-Coria, Hilda LaFerla, Frank M. |
author_sort |
Chabrier, Meredith A. |
title |
Soluble Aβ Promotes Wild-Type Tau Pathology in vivo |
title_short |
Soluble Aβ Promotes Wild-Type Tau Pathology in vivo |
title_full |
Soluble Aβ Promotes Wild-Type Tau Pathology in vivo |
title_fullStr |
Soluble Aβ Promotes Wild-Type Tau Pathology in vivo |
title_full_unstemmed |
Soluble Aβ Promotes Wild-Type Tau Pathology in vivo |
title_sort |
soluble aβ promotes wild-type tau pathology in vivo |
publishDate |
2012 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586232 http://www.ncbi.nlm.nih.gov/pubmed/23197725 https://doi.org/10.1523/JNEUROSCI.0172-12.2012 |
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Arctic |
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Arctic |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586232 http://www.ncbi.nlm.nih.gov/pubmed/23197725 http://dx.doi.org/10.1523/JNEUROSCI.0172-12.2012 |
op_doi |
https://doi.org/10.1523/JNEUROSCI.0172-12.2012 |
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Journal of Neuroscience |
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32 |
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48 |
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17345 |
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17350 |
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1766337351827587072 |