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dc.contributor.authorTai, Hwan-Chingen_US
dc.contributor.authorWang, Bo Yen_US
dc.contributor.authorSerrano–Pozo, Albertoen_US
dc.contributor.authorFrosch, Matthew Pen_US
dc.contributor.authorSpires-Jones, Tara Len_US
dc.contributor.authorHyman, Bradley Ten_US
dc.date.accessioned2014-11-03T17:40:20Z
dc.date.issued2014en_US
dc.identifier.citationTai, Hwan-Ching, Bo Y Wang, Alberto Serrano–Pozo, Matthew P Frosch, Tara L Spires-Jones, and Bradley T Hyman. 2014. “Frequent and symmetric deposition of misfolded tau oligomers within presynaptic and postsynaptic terminals in Alzheimer’s disease.” Acta Neuropathologica Communications 2 (1): 146. doi:10.1186/s40478-014-0146-2. http://dx.doi.org/10.1186/s40478-014-0146-2.en
dc.identifier.issn2051-5960en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13347600
dc.description.abstractThe accumulation of neurofibrillary tangles in Alzheimer’s disease (AD) propagates with characteristic spatiotemporal patterns which follow brain network connections, implying trans-synaptic transmission of tauopathy. Since misfolded tau has been shown to transmit across synapses in AD animal models, we hypothesized that synapses in AD patients may contain misfolded tau. By immunofluorescence imaging of bipartite synapses from AD subjects, we detected tau protein in 38.4% of presynaptic and 50.9% of postsynaptic terminals. The pre/post distribution for hyperphosphorylated tau was 26.9%/30.7%, and for misfolded tau 18.3%/19.3%. In the temporal cortex, microscopic aggregates of tau, containing ultra-stable oligomers, were estimated to accumulate within trillions of synapses, outnumbering macroscopic tau aggregates such as tangles by 10000 fold. Non-demented elderly also showed considerable synaptic tau hyperphosphorylation and some misfolding, implicating the synapse as one of the first subcellular compartments affected by tauopathy. Misfolding of tau protein appeared to occur in situ inside synaptic terminals, without mislocalizing or mistrafficking. Misfolded tau at synapses may represent early signs of neuronal degeneration, mediators of synaptotoxicity, and anatomical substrates for transmitting tauopathy, but its actual role in these processes remain to be elucidated. Electronic supplementary material The online version of this article (doi:10.1186/s40478-014-0146-2) contains supplementary material, which is available to authorized users.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/s40478-014-0146-2en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209049/pdf/en
dash.licenseLAAen_US
dc.titleFrequent and symmetric deposition of misfolded tau oligomers within presynaptic and postsynaptic terminals in Alzheimer’s diseaseen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalActa Neuropathologica Communicationsen
dash.depositing.authorFrosch, Matthew Pen_US
dc.date.available2014-11-03T17:40:20Z
dc.identifier.doi10.1186/s40478-014-0146-2*
dash.contributor.affiliatedFrosch, Matthew
dash.contributor.affiliatedHyman, Bradley


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