<> <http://www.w3.org/2000/01/rdf-schema#comment> "The repository administrator has not yet configured an RDF license."^^<http://www.w3.org/2001/XMLSchema#string> . <> <http://xmlns.com/foaf/0.1/primaryTopic> <https://discovery.ucl.ac.uk/id/eprint/10110692> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/AcademicArticle> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Article> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/title> "Fibrillation and molecular characteristics are coherent with clinical and pathological features of 4-repeat tauopathy caused by MAPT variant G273R"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/abstract> "Microtubule Associated Protein Tau (MAPT) forms proteopathic aggregates in several diseases. The G273R tau mutant, located in the first repeat region, was found by exome sequencing in a patient who presented with dementia and parkinsonism. We herein return to pathological examination which demonstrated tau immunoreactivity in neurons and glia consistent of mixed progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) features. To rationalize the pathological findings, we used molecular biophysics to characterize the mutation in more detail in vitro and in Drosophila. The G273R mutation increases the aggregation propensity of 4-repeat (4R) tau and alters the tau binding affinity towards microtubules (MTs) and F-actin. Tau aggregates in PSP and CBD are predominantly 4R tau. Our data suggest that the G273R mutation induces a shift in pool of 4R tau by lower F-actin affinity, alters the conformation of MT bound 4R tau, while increasing chaperoning of 3R tau by binding stronger to F-actin. The mutation augmented fibrillation of 4R tau initiation in vitro and in glial cells in Drosophila and showed preferential seeding of 4R tau in vitro suggestively causing a late onset 4R tauopathy reminiscent of PSP and CBD."^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/date> "2020-12" . <https://discovery.ucl.ac.uk/id/document/1191798> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Document> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/volume> "146" . <https://discovery.ucl.ac.uk/id/publication/ext-abc2dab7438c66b3af1d1ea89016459f> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Collection> . <https://discovery.ucl.ac.uk/id/publication/ext-abc2dab7438c66b3af1d1ea89016459f> <http://xmlns.com/foaf/0.1/name> "Neurobiology of Disease"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/isPartOf> <https://discovery.ucl.ac.uk/id/publication/ext-abc2dab7438c66b3af1d1ea89016459f> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/status> <http://purl.org/ontology/bibo/status/published> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-376ef188e48e0aaccfdfd2f2a790b336> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_1> <https://discovery.ucl.ac.uk/id/person/ext-376ef188e48e0aaccfdfd2f2a790b336> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-91b486bba5bd62bc8b389ab98d46d8de> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_2> <https://discovery.ucl.ac.uk/id/person/ext-91b486bba5bd62bc8b389ab98d46d8de> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-5e4d2221e596f5afef78d54a41273d1b> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_3> <https://discovery.ucl.ac.uk/id/person/ext-5e4d2221e596f5afef78d54a41273d1b> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-3a3c105137de30ceaf8093e0cb958a5c> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_4> <https://discovery.ucl.ac.uk/id/person/ext-3a3c105137de30ceaf8093e0cb958a5c> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-bfc286990e41872e05dd76242c9d5807> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_5> <https://discovery.ucl.ac.uk/id/person/ext-bfc286990e41872e05dd76242c9d5807> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-8456dcf6d081d6d787a5ab22405145d0> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_6> <https://discovery.ucl.ac.uk/id/person/ext-8456dcf6d081d6d787a5ab22405145d0> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-8e322b4994b2ee704129e475c529bd4f> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_7> <https://discovery.ucl.ac.uk/id/person/ext-8e322b4994b2ee704129e475c529bd4f> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-310ff5c4cddd8778292fba51a10e9775> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_8> <https://discovery.ucl.ac.uk/id/person/ext-310ff5c4cddd8778292fba51a10e9775> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-46ef8725b099e245f47a3974a7311ebf> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_9> <https://discovery.ucl.ac.uk/id/person/ext-46ef8725b099e245f47a3974a7311ebf> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-f763c68f4b2c0fa8343cbb823efbbf19> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_10> <https://discovery.ucl.ac.uk/id/person/ext-f763c68f4b2c0fa8343cbb823efbbf19> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-7582ec038dd04b9bad23b0015faf27aa> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_11> <https://discovery.ucl.ac.uk/id/person/ext-7582ec038dd04b9bad23b0015faf27aa> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-74e2f0b2f58f9394f9184beef1b076ad> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_12> <https://discovery.ucl.ac.uk/id/person/ext-74e2f0b2f58f9394f9184beef1b076ad> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-52f3c625438deae1a0340c2d88d2fe9a> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_13> <https://discovery.ucl.ac.uk/id/person/ext-52f3c625438deae1a0340c2d88d2fe9a> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-247a7f7726a59bb07faed886ccd6017d> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_14> <https://discovery.ucl.ac.uk/id/person/ext-247a7f7726a59bb07faed886ccd6017d> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-dc867023aaf2ade789dea908ab097452> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_15> <https://discovery.ucl.ac.uk/id/person/ext-dc867023aaf2ade789dea908ab097452> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-72e0912c7a37dc532e522c39ea4239a3> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_16> <https://discovery.ucl.ac.uk/id/person/ext-72e0912c7a37dc532e522c39ea4239a3> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-d46428199238161c08c12330789ec66a> . <https://discovery.ucl.ac.uk/id/eprint/10110692> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> . <https://discovery.ucl.ac.uk/id/eprint/10110692#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_17> <https://discovery.ucl.ac.uk/id/person/ext-d46428199238161c08c12330789ec66a> . <https://discovery.ucl.ac.uk/id/person/ext-376ef188e48e0aaccfdfd2f2a790b336> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-376ef188e48e0aaccfdfd2f2a790b336> <http://xmlns.com/foaf/0.1/givenName> "A"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-376ef188e48e0aaccfdfd2f2a790b336> <http://xmlns.com/foaf/0.1/familyName> "Sandberg"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-376ef188e48e0aaccfdfd2f2a790b336> <http://xmlns.com/foaf/0.1/name> "A Sandberg"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-8456dcf6d081d6d787a5ab22405145d0> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-8456dcf6d081d6d787a5ab22405145d0> <http://xmlns.com/foaf/0.1/givenName> "L"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-8456dcf6d081d6d787a5ab22405145d0> <http://xmlns.com/foaf/0.1/familyName> "R'Bibo"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-8456dcf6d081d6d787a5ab22405145d0> <http://xmlns.com/foaf/0.1/name> "L R'Bibo"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-91b486bba5bd62bc8b389ab98d46d8de> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-91b486bba5bd62bc8b389ab98d46d8de> <http://xmlns.com/foaf/0.1/givenName> "H"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-91b486bba5bd62bc8b389ab98d46d8de> <http://xmlns.com/foaf/0.1/familyName> "Ling"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-91b486bba5bd62bc8b389ab98d46d8de> <http://xmlns.com/foaf/0.1/name> "H Ling"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-74e2f0b2f58f9394f9184beef1b076ad> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-74e2f0b2f58f9394f9184beef1b076ad> <http://xmlns.com/foaf/0.1/givenName> "S"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-74e2f0b2f58f9394f9184beef1b076ad> <http://xmlns.com/foaf/0.1/familyName> "Nyström"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-74e2f0b2f58f9394f9184beef1b076ad> <http://xmlns.com/foaf/0.1/name> "S Nyström"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-72e0912c7a37dc532e522c39ea4239a3> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-72e0912c7a37dc532e522c39ea4239a3> <http://xmlns.com/foaf/0.1/givenName> "T"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-72e0912c7a37dc532e522c39ea4239a3> <http://xmlns.com/foaf/0.1/familyName> "Revesz"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-72e0912c7a37dc532e522c39ea4239a3> <http://xmlns.com/foaf/0.1/name> "T Revesz"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-d46428199238161c08c12330789ec66a> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-d46428199238161c08c12330789ec66a> <http://xmlns.com/foaf/0.1/givenName> "KY"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-d46428199238161c08c12330789ec66a> <http://xmlns.com/foaf/0.1/familyName> "Mok"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-d46428199238161c08c12330789ec66a> <http://xmlns.com/foaf/0.1/name> "KY Mok"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-52f3c625438deae1a0340c2d88d2fe9a> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . 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