| Synaptic alterations in the rTg4510 mouse model of tauopathy. | |
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MedLine Citation:
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PMID: 23047530 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Synapse loss, rather than the hallmark amyloid-β (Aβ) plaques or tau filled neurofibrillary tangles (NFT), is considered the most predictive pathological feature associated with cognitive status in the Alzheimer disease (AD) brain. The role of Aβ in synapse loss is well established, but despite data linking tau to synaptic function, the role of tau in synapse loss remains largely undetermined. Here we test the hypothesis that human mutant P301L tau over-expression in a mouse model (rTg4510) will lead to age-dependent synaptic loss and dysfunction. Using array tomography and two methods of quantification (automated, threshold-based counting and a manual stereology based technique) we demonstrate that overall synapse density is maintained in the neuropil, implicating synapse loss commensurate with the cortical atrophy known to occur in this model. Multi-photon in-vivo imaging reveals close to 30% loss of apical dendritic spines of individual pyramidal neurons suggesting these cells may be particularly vulnerable to tau-induced degeneration. Post-mortem, we confirm the presence of tau in dendritic spines of rTg4510-YFP mouse brain by array tomography. These data implicate tau-induced loss of a subset of synapses that may be accompanied by compensatory increases in other synaptic subtypes thereby preserving overall synapse density. Biochemical fractionation of synaptosomes from rTg4510 brain demonstrates a significant decrease in expression of several synaptic proteins, suggesting a functional deficit of remaining synapses in the rTg4510 brain. Together these data show morphological and biochemical synaptic consequences in response to tau over-expression in the rTg4510 mouse model. J. Comp. Neurol., 2012. © 2012 Wiley Periodicals, Inc. |
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Authors:
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Katherine J Kopeikina; Manuela Polydoro; Hwan-Ching Tai; Erich Yaeger; George A Carlson; Rose Pitstick; Bradley T Hyman; Tara L Spires-Jones |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-10 |
Journal Detail:
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Title: The Journal of comparative neurology Volume: - ISSN: 1096-9861 ISO Abbreviation: J. Comp. Neurol. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0406041 Medline TA: J Comp Neurol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Wiley Periodicals, Inc. |
Affiliation:
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Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston Massachusetts 02118, USA; MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown Massachusetts 02129, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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