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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2010-12-21
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pubmed:abstractText |
The microtubule-associated protein tau accumulates in Alzheimer's and other fatal dementias, which manifest when forebrain neurons die. Recent advances in understanding these disorders indicate that brain dysfunction precedes neurodegeneration, but the role of tau is unclear. Here, we show that early tau-related deficits develop not from the loss of synapses or neurons, but rather as a result of synaptic abnormalities caused by the accumulation of hyperphosphorylated tau within intact dendritic spines, where it disrupts synaptic function by impairing glutamate receptor trafficking or synaptic anchoring. Mutagenesis of 14 disease-associated serine and threonine amino acid residues to create pseudohyperphosphorylated tau caused tau mislocalization while creation of phosphorylation-deficient tau blocked the mistargeting of tau to dendritic spines. Thus, tau phosphorylation plays a critical role in mediating tau mislocalization and subsequent synaptic impairment. These data establish that the locus of early synaptic malfunction caused by tau resides in dendritic spines.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/K02 DA025048-04,
http://linkedlifedata.com/resource/pubmed/grant/K02-DA025048,
http://linkedlifedata.com/resource/pubmed/grant/P30 CA77598,
http://linkedlifedata.com/resource/pubmed/grant/R01 AG026252-05,
http://linkedlifedata.com/resource/pubmed/grant/R01 DA020582-04S1,
http://linkedlifedata.com/resource/pubmed/grant/R01 DA020582-05,
http://linkedlifedata.com/resource/pubmed/grant/R01 NS049178-05,
http://linkedlifedata.com/resource/pubmed/grant/R01 NS049178-05S1,
http://linkedlifedata.com/resource/pubmed/grant/R01 NS063214-03,
http://linkedlifedata.com/resource/pubmed/grant/R01 NS063214-04,
http://linkedlifedata.com/resource/pubmed/grant/R01-AG026252,
http://linkedlifedata.com/resource/pubmed/grant/R01-DA020582,
http://linkedlifedata.com/resource/pubmed/grant/R01-NS049129,
http://linkedlifedata.com/resource/pubmed/grant/R01-NS049178,
http://linkedlifedata.com/resource/pubmed/grant/R01-NS063214,
http://linkedlifedata.com/resource/pubmed/grant/T32 DA022616-02,
http://linkedlifedata.com/resource/pubmed/grant/T32-DA007234
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1097-4199
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pubmed:author |
pubmed-author:AsheKaren HKH,
pubmed-author:BUKINIuIu,
pubmed-author:CarlsonGeorge AGA,
pubmed-author:GrantMarianne KMK,
pubmed-author:HooverBrian RBR,
pubmed-author:KotilinekLinda ALA,
pubmed-author:LanierLorene MLM,
pubmed-author:PenrodRachel DRD,
pubmed-author:PitstickRoseR,
pubmed-author:ReedMiranda NMN,
pubmed-author:SuJianjunJ,
pubmed-author:YuanLi-LianLL
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
22
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pubmed:volume |
68
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1067-81
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pubmed:dateRevised |
2011-10-6
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pubmed:meshHeading |
pubmed-meshheading:21172610-Animals,
pubmed-meshheading:21172610-Cells, Cultured,
pubmed-meshheading:21172610-Dendritic Spines,
pubmed-meshheading:21172610-Memory Disorders,
pubmed-meshheading:21172610-Mice,
pubmed-meshheading:21172610-Mice, Transgenic,
pubmed-meshheading:21172610-Nerve Degeneration,
pubmed-meshheading:21172610-Phosphorylation,
pubmed-meshheading:21172610-Rats,
pubmed-meshheading:21172610-Synapses,
pubmed-meshheading:21172610-tau Proteins
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pubmed:year |
2010
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pubmed:articleTitle |
Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration.
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pubmed:affiliation |
Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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