Frequent and symmetric deposition of misfolded tau oligomers within presynaptic and postsynaptic terminals in Alzheimer’s disease

DSpace/Manakin Repository

Frequent and symmetric deposition of misfolded tau oligomers within presynaptic and postsynaptic terminals in Alzheimer’s disease

Show simple item record

dc.contributor.author Tai, Hwan-Ching en_US
dc.contributor.author Wang, Bo Y en_US
dc.contributor.author Serrano–Pozo, Alberto en_US
dc.contributor.author Frosch, Matthew P en_US
dc.contributor.author Spires-Jones, Tara L en_US
dc.contributor.author Hyman, Bradley T en_US
dc.date.accessioned 2014-11-03T17:40:20Z
dc.date.issued 2014 en_US
dc.identifier.citation Tai, 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.issn 2051-5960 en
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:13347600
dc.description.abstract The 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.iso en_US en
dc.publisher BioMed Central en
dc.relation.isversionof doi:10.1186/s40478-014-0146-2 en
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209049/pdf/ en
dash.license LAA en_US
dc.title Frequent and symmetric deposition of misfolded tau oligomers within presynaptic and postsynaptic terminals in Alzheimer’s disease en
dc.type Journal Article en_US
dc.description.version Version of Record en
dc.relation.journal Acta Neuropathologica Communications en
dash.depositing.author Frosch, Matthew P en_US
dc.date.available 2014-11-03T17:40:20Z

Files in this item

Files Size Format View
4209049.pdf 3.397Mb PDF View/Open

This item appears in the following Collection(s)

Show simple item record

 
 

Search DASH


Advanced Search
 
 

Submitters