{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:40:24Z","timestamp":1791232824612,"version":"4.1.0"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T00:00:00Z","timestamp":1465257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurobiology of Disease"],"published-print":{"date-parts":[[2016,10]]},"DOI":"10.1016\/j.nbd.2016.05.016","type":"journal-article","created":{"date-parts":[[2016,5,31]],"date-time":"2016-05-31T15:49:54Z","timestamp":1464709794000},"page":"18-31","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":90,"special_numbering":"C","title":["Pathological conformations involving the amino terminus of tau occur early in Alzheimer's disease and are differentially detected by monoclonal antibodies"],"prefix":"10.1016","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3136-7545","authenticated-orcid":false,"given":"Benjamin","family":"Combs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsey","family":"Hamel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M.","family":"Kanaan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.nbd.2016.05.016_bb0005","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s004010100423","article-title":"Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease","volume":"103","author":"Augustinack","year":"2002","journal-title":"Acta Neuropathol. (Berl.)"},{"key":"10.1016\/j.nbd.2016.05.016_bb0010","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/0006-8993(89)91396-6","article-title":"Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease","volume":"477","author":"Bancher","year":"1989","journal-title":"Brain Res."},{"key":"10.1016\/j.nbd.2016.05.016_bb0015","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0006-8993(91)90681-K","article-title":"Abnormal phosphorylation of tau precedes ubiquitination in neurofibrillary pathology of Alzheimer disease","volume":"539","author":"Bancher","year":"1991","journal-title":"Brain Res."},{"key":"10.1016\/j.nbd.2016.05.016_bb0020","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1023\/B:NEUR.0000044190.96426.b9","article-title":"Tau epitope display in progressive supranuclear palsy and corticobasal degeneration","volume":"33","author":"Berry","year":"2004","journal-title":"J. Neurocytol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0025","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1097\/00005072-199704000-00010","article-title":"Relationships between regional neuronal loss and neurofibrillary changes in the hippocampal formation and duration and severity of Alzheimer disease","volume":"56","author":"Bobinski","year":"1997","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0030","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1097\/00005072-199403000-00007","article-title":"Immunohistochemical staging of neurofibrillary degeneration in Alzheimer's disease","volume":"53","author":"Bondareff","year":"1994","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0035","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0040","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1007\/BF00293315","article-title":"A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads","volume":"87","author":"Braak","year":"1994","journal-title":"Acta Neuropathol. (Berl.)"},{"key":"10.1016\/j.nbd.2016.05.016_bb0045","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1083\/jcb.131.5.1327","article-title":"Interaction of tau with the neural plasma membrane mediated by tau's amino-terminal projection domain","volume":"131","author":"Brandt","year":"1995","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0050","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0306-4522(02)00942-9","article-title":"Stereologic analysis of neurofibrillary tangle formation in prefrontal cortex area 9 in aging and Alzheimer's disease","volume":"117","author":"Bussiere","year":"2003","journal-title":"Neuroscience"},{"key":"10.1016\/j.nbd.2016.05.016_bb0055","doi-asserted-by":"crossref","first-page":"32789","DOI":"10.1074\/jbc.271.51.32789","article-title":"The structural basis of monoclonal antibody Alz50's selectivity for Alzheimer's disease pathology","volume":"271","author":"Carmel","year":"1996","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.nbd.2016.05.016_bb0060","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1007\/BF00227736","article-title":"Immunocytochemistry of neurofibrillary tangles with antibodies to subregions of tau protein: identification of hidden and cleaved tau epitopes and a new phosphorylation site","volume":"84","author":"Dickson","year":"1992","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0065","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/0006-8993(93)91707-Y","article-title":"Lack of the carboxyl terminal sequence of tau in ghost tangles of Alzheimer's disease","volume":"601","author":"Endoh","year":"1993","journal-title":"Brain Res."},{"key":"10.1016\/j.nbd.2016.05.016_bb0070","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.bbadis.2004.08.013","article-title":"Potential structure\/function relationships of predicted secondary structural elements of tau","volume":"1739","author":"Gamblin","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.nbd.2016.05.016_bb0075","doi-asserted-by":"crossref","first-page":"6136","DOI":"10.1021\/bi000201f","article-title":"In vitro polymerization of tau protein monitored by laser light scattering: method and application to the study of FTDP-17 mutants","volume":"39","author":"Gamblin","year":"2000","journal-title":"Biochemistry"},{"key":"10.1016\/j.nbd.2016.05.016_bb0080","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s004010051189","article-title":"The extent of neurofibrillary pathology in perforant pathway neurons is the key determinant of dementia in the very old","volume":"100","author":"Garcia-Sierra","year":"2000","journal-title":"Acta Neuropathol. (Berl.)"},{"key":"10.1016\/j.nbd.2016.05.016_bb0085","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3233\/JAD-2003-5201","article-title":"Conformational changes and truncation of tau protein during tangle evolution in Alzheimer's disease","volume":"5","author":"Garcia-Sierra","year":"2003","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.nbd.2016.05.016_bb0090","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1006\/exnr.2002.8014","article-title":"Tau conformational changes correspond to impairments of episodic memory in mild cognitive impairment and Alzheimer's disease","volume":"177","author":"Ghoshal","year":"2002","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0095","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0304-3940(95)11484-E","article-title":"Monoclonal antibody AT8 recognises tau protein phosphorylated at both serine 202 and threonine 205","volume":"189","author":"Goedert","year":"1995","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.nbd.2016.05.016_bb0100","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/ana.410410106","article-title":"Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease","volume":"41","author":"Gomez-Isla","year":"1997","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0105","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S0021-9258(18)48531-6","article-title":"Hydrofluoric acid-treated tau PHF proteins display the same biochemical properties as normal tau","volume":"267","author":"Greenberg","year":"1992","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.nbd.2016.05.016_bb0110","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0002-9440(10)63317-2","article-title":"Active caspase-6 and caspase-6-cleaved tau in neuropil threads, neuritic plaques, and neurofibrillary tangles of Alzheimer's disease","volume":"165","author":"Guo","year":"2004","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0115","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/0161-5890(86)90122-7","article-title":"Use of monoclonal antibodies to detect conformational alterations in lactate dehydrogenase isoenzyme 5 on heat denaturation and on adsorption to polystyrene plates","volume":"23","author":"Hollander","year":"1986","journal-title":"Mol. Immunol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0120","doi-asserted-by":"crossref","first-page":"7895","DOI":"10.1523\/JNEUROSCI.1988-04.2004","article-title":"Early N-terminal changes and caspase-6 cleavage of tau in Alzheimer's disease","volume":"24","author":"Horowitz","year":"2004","journal-title":"J. Neurosci."},{"key":"10.1016\/j.nbd.2016.05.016_bb0125","doi-asserted-by":"crossref","first-page":"12859","DOI":"10.1021\/bi061325g","article-title":"N-terminal fragments of tau inhibit full-length tau polymerization in vitro","volume":"45","author":"Horowitz","year":"2006","journal-title":"Biochemistry"},{"key":"10.1016\/j.nbd.2016.05.016_bb0130","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/ana.410230410","article-title":"Alz-50 antibody recognizes Alzheimer-related neuronal changes","volume":"23","author":"Hyman","year":"1988","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0135","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1021\/bi0521543","article-title":"Global hairpin folding of tau in solution","volume":"45","author":"Jeganathan","year":"2006","journal-title":"Biochemistry"},{"key":"10.1016\/j.nbd.2016.05.016_bb0140","doi-asserted-by":"crossref","first-page":"32066","DOI":"10.1074\/jbc.M805300200","article-title":"Proline-directed pseudo-phosphorylation at AT8 and PHF1 epitopes induces a compaction of the paperclip folding of tau and generates a pathological (MC-1) conformation","volume":"283","author":"Jeganathan","year":"2008","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.nbd.2016.05.016_bb0145","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/(SICI)1097-4547(19970415)48:2<128::AID-JNR5>3.0.CO;2-E","article-title":"Alz-50 and MC-1, a new monoclonal antibody raised to paired helical filaments, recognize conformational epitopes on recombinant tau","volume":"48","author":"Jicha","year":"1997","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.nbd.2016.05.016_bb0150","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/(SICI)1097-4547(19990315)55:6<713::AID-JNR6>3.0.CO;2-G","article-title":"Sequence requirements for formation of conformational variants of tau similar to those found in Alzheimer's disease","volume":"55","author":"Jicha","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.nbd.2016.05.016_bb0155","doi-asserted-by":"crossref","first-page":"9858","DOI":"10.1523\/JNEUROSCI.0560-11.2011","article-title":"Pathogenic forms of tau inhibit kinesin-dependent axonal transport through a mechanism involving activation of axonal phosphotransferases","volume":"31","author":"Kanaan","year":"2011","journal-title":"J. Neurosci."},{"issue":"826","key":"10.1016\/j.nbd.2016.05.016_bb0160","first-page":"e15","article-title":"Phosphorylation in the amino terminus of tau prevents inhibition of anterograde axonal transport","volume":"33","author":"Kanaan","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.nbd.2016.05.016_bb0165","article-title":"Characterization of early pathological tau conformations and phosphorylation in chronic traumatic encephalopathy","author":"Kanaan","year":"2015","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0170","doi-asserted-by":"crossref","first-page":"220","DOI":"10.3109\/10520299509108199","article-title":"DAPI: a DNA-specific fluorescent probe","volume":"70","author":"Kapuscinski","year":"1995","journal-title":"Biotech. Histochem."},{"key":"10.1016\/j.nbd.2016.05.016_bb0175","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/jnr.21850","article-title":"The amino terminus of tau inhibits kinesin-dependent axonal transport: implications for filament toxicity","volume":"87","author":"LaPointe","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.nbd.2016.05.016_bb0180","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3233\/JAD-2007-12410","article-title":"Earliest stages of tau conformational changes are related to the appearance of a sequence of specific phospho-dependent tau epitopes in Alzheimer's disease","volume":"12","author":"Luna-Munoz","year":"2007","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.nbd.2016.05.016_bb0185","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/BF00294259","article-title":"Monitoring pathological assembly of tau and beta-amyloid proteins in Alzheimer's disease","volume":"89","author":"Mena","year":"1995","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0190","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/BF00227819","article-title":"Monoclonal antibodies with selective specificity for Alzheimer tau are directed against phosphatase-sensitive epitopes","volume":"84","author":"Mercken","year":"1992","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0195","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1097\/00005072-199902000-00008","article-title":"Neurons may live for decades with neurofibrillary tangles","volume":"58","author":"Morsch","year":"1999","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0200","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1000034","article-title":"Structural polymorphism of 441-residue tau at single residue resolution","volume":"7","author":"Mukrasch","year":"2009","journal-title":"PLoS Biol."},{"key":"10.1016\/j.nbd.2016.05.016_bb0205","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1002\/jnr.490390607","article-title":"Monoclonal antibody PHF-1 recognizes tau protein phosphorylated at serine residues 396 and 404","volume":"39","author":"Otvos","year":"1994","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.nbd.2016.05.016_bb0210","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/cm.970080303","article-title":"Phosphorylation determines two distinct species of tau in the central nervous system","volume":"8","author":"Papasozomenos","year":"1987","journal-title":"Cell Motil. Cytoskeleton"},{"key":"10.1016\/j.nbd.2016.05.016_bb9000","doi-asserted-by":"crossref","first-page":"23063","DOI":"10.1074\/jbc.M111.237974","article-title":"Characterization of prefibrillar Tau oligomers in vitro and in Alzheimer disease","volume":"286","author":"Patterson","year":"2011","journal-title":"J Biol Chem."},{"key":"10.1016\/j.nbd.2016.05.016_bb9005","doi-asserted-by":"crossref","first-page":"10300","DOI":"10.1021\/bi2009147","article-title":"Heat shock protein 70 prevents both tau aggregation and the inhibitory effects of preexisting tau aggregates on fast axonal transport","volume":"50","author":"Patterson","year":"2011","journal-title":"Biochemistry."},{"key":"10.1016\/j.nbd.2016.05.016_bb0215","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0094251","article-title":"Specificity of anti-tau antibodies when analyzing mice models of Alzheimer's disease: problems and solutions","volume":"9","author":"Petry","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.nbd.2016.05.016_bb0220","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1126\/science.1113694","article-title":"Tau suppression in a neurodegenerative mouse model improves memory function","volume":"309","author":"Santacruz","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.nbd.2016.05.016_bb0225","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0022-1759(91)90152-6","article-title":"An appraisal of polystyrene-(ELISA) and nitrocellulose-based (ELIFA) enzyme immunoassay systems using monoclonal antibodies reactive toward antigenically distinct forms of human C-reactive protein","volume":"141","author":"Shields","year":"1991","journal-title":"J. Immunol. Methods"},{"key":"10.1016\/j.nbd.2016.05.016_bb0230","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1523\/JNEUROSCI.3072-08.2008","article-title":"In vivo imaging reveals dissociation between caspase activation and acute neuronal death in tangle-bearing neurons","volume":"28","author":"Spires-Jones","year":"2008","journal-title":"J. Neurosci."},{"key":"10.1016\/j.nbd.2016.05.016_bb0235","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1126\/science.1062382","article-title":"Tauopathy in drosophila: neurodegeneration without neurofibrillary tangles","volume":"293","author":"Wittmann","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.nbd.2016.05.016_bb0240","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","article-title":"Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model","volume":"53","author":"Yoshiyama","year":"2007","journal-title":"Neuron"}],"container-title":["Neurobiology of Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S096999611630119X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S096999611630119X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T18:04:39Z","timestamp":1656612279000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S096999611630119X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":50,"alternative-id":["S096999611630119X"],"URL":"https:\/\/doi.org\/10.1016\/j.nbd.2016.05.016","relation":{},"ISSN":["0969-9961"],"issn-type":[{"value":"0969-9961","type":"print"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pathological conformations involving the amino terminus of tau occur early in Alzheimer's disease and are differentially detected by monoclonal antibodies","name":"articletitle","label":"Article Title"},{"value":"Neurobiology of Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.nbd.2016.05.016","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}