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dc.contributor.authorFalcon, Benjamin
dc.contributor.authorZhang, Wenjuan
dc.contributor.authorSchweighauser, Manuel
dc.contributor.authorMurzin, Alexey G
dc.contributor.authorVidal, Ruben
dc.contributor.authorGarringer, Holly J
dc.contributor.authorGhetti, Bernardino
dc.contributor.authorScheres, Sjors HW
dc.contributor.authorGoedert, Michel
dc.date.accessioned2018-11-27T15:25:19Z
dc.date.available2018-11-27T15:25:19Z
dc.date.issued2018-11
dc.identifier.issn0001-6322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/286006
dc.description.abstractThe ordered assembly of tau protein into abnormal filaments is a defining characteristic of Alzheimer's disease (AD) and other neurodegenerative disorders. It is not known if the structures of tau filaments vary within, or between, the brains of individuals with AD. We used a combination of electron cryo-microscopy (cryo-EM) and immuno-gold negative-stain electron microscopy (immuno-EM) to determine the structures of paired helical filaments (PHFs) and straight filaments (SFs) from the frontal cortex of 17 cases of AD (15 sporadic and 2 inherited) and 2 cases of atypical AD (posterior cortical atrophy). The high-resolution structures of PHFs and SFs from the frontal cortex of 3 cases of AD, 2 sporadic and 1 inherited, were determined by cryo-EM. We also used immuno-EM to study the PHFs and SFs from a number of cortical and subcortical brain regions. PHFs outnumbered SFs in all AD cases. By cryo-EM, PHFs and SFs were made of two C-shaped protofilaments with a combined cross-β/β-helix structure, as described previously for one case of AD. The higher resolution structures obtained here showed two additional amino acids at each end of the protofilament. The immuno-EM findings, which indicated the presence of repeats 3 and 4, but not of the N-terminal regions of repeats 1 and 2, of tau in the filament cores of all AD cases, were consistent with the cryo-EM results. These findings show that there is no significant variation in tau filament structures between individuals with AD. This knowledge will be crucial for understanding the mechanisms that underlie tau filament formation and for developing novel diagnostics and therapies.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleTau filaments from multiple cases of sporadic and inherited Alzheimer's disease adopt a common fold.
dc.typeArticle
prism.endingPage708
prism.issueIdentifier5
prism.publicationDate2018
prism.publicationNameActa Neuropathol
prism.startingPage699
prism.volume136
dc.identifier.doi10.17863/CAM.33326
pubs.declined2018-11-27T15:22:19.627+0000
dcterms.dateAccepted2018-09-20
rioxxterms.versionofrecord10.1007/s00401-018-1914-z
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-11
dc.contributor.orcidFalcon, Benjamin [0000-0002-8176-2618]
dc.contributor.orcidSchweighauser, Manuel [0000-0002-1848-1610]
dc.contributor.orcidVidal, Ruben [0000-0002-5803-3871]
dc.contributor.orcidGhetti, Bernardino [0000-0002-1842-8019]
dc.contributor.orcidScheres, Sjors HW [0000-0002-0462-6540]
dc.contributor.orcidGoedert, Michel [0000-0002-5214-7886]
dc.identifier.eissn1432-0533
rioxxterms.typeJournal Article/Review
cam.issuedOnline2018-10-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International