{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T06:28:08Z","timestamp":1785911288787,"version":"3.56.0"},"reference-count":73,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,6,28]]},"abstract":"<jats:p>Background: Deposits of hyperphosphorylated tau fibrils are hallmarks of a broad spectrum of tauopathies, including Alzheimer\u2019s disease (AD). Objective: To investigate heterogeneity of tau pathology across brain extracts from a broad selection of different tauopathies and examine the binding properties of the humanized pS396-tau antibody hC10.2 and six other anti-tau antibodies. Methods: 76 individual tauopathy tissue samples were analyzed in a battery of assays: immunohistochemistry, ELISA, tau aggregation assay, western blot, [3H]PI-2620 and [3H]MK-6240 tau tracer binding, and aggregated seeding activity in RD_P301S HEK293T Biosensor cells. The efficiency of seven anti-tau antibodies to engage with pathological tau species was directly compared. Results: Our data indicate that a strong correlation existed between the tau tracer binding, amount of tau aggregates, pS396-tau phosphorylation, and seeding activity. The hC10.2 antibody, which has entered clinical development, effectively engaged with its epitope across all individual cases of mid-stage and late AD, and primary tauopathies. hC10.2 was superior compared to other phospho- and total tau antibodies to prevent seeded tau aggregation in the biosensor cells. hC10.2 effectively depleted hyperphosphorylated and aggregated tau species across all tauopathy samples proportionally to the amount of tau aggregates. In AD samples, hC10.2 bound to ghost tangles which represent extracellular pathological tau species. Conclusion: S396 hyperphosphorylation is a feature of the formation of seeding-competent tau across different tauopathies and it is present both in intra- and extracellular pathological tau. hC10.2 represents an excellent candidate for a hyperphosphorylation-selective therapeutic tau antibody for the treatment of AD and primary tauopathies.<\/jats:p>","DOI":"10.3233\/jad-220125","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T12:22:56Z","timestamp":1652185376000},"page":"207-228","source":"Crossref","is-referenced-by-count":18,"title":["Highly Specific and Sensitive Target Binding by the Humanized pS396-Tau Antibody hC10.2 Across a Wide Spectrum of Alzheimer\u2019s Disease and Primary Tauopathy Postmortem Brains"],"prefix":"10.1177","volume":"88","author":[{"given":"Lone","family":"Helboe","sequence":"first","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Rosenqvist","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Volbracht","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars \u00d8.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan T.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren","family":"Christensen","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Egebjerg","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus T.","family":"Christoffersen","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benny","family":"Bang-Andersen","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Beach","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute, Sun City, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geidy E.","family":"Serrano","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute, Sun City, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeppe","family":"Falsig","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S, Valby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-220125_ref1","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1146\/annurev.neuro.24.1.1121","article-title":"Neurodegenerative tauopathies","volume":"24","author":"Lee","year":"2001","journal-title":"Annu Rev Neurosci"},{"key":"10.3233\/JAD-220125_ref2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13024-017-0192-x","article-title":"Glial contributions to neurodegeneration in tauopathies","volume":"12","author":"Leyns","year":"2017","journal-title":"Mol Neurodegener"},{"key":"10.3233\/JAD-220125_ref3","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/S1474-4422(13)70090-5","article-title":"Tau pathology and neurodegeneration","volume":"12","author":"Spillantini","year":"2013","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-220125_ref4","doi-asserted-by":"crossref","first-page":"5827","DOI":"10.1073\/pnas.87.15.5827","article-title":"A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis","volume":"87","author":"Greenberg","year":"1990","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-220125_ref5","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/0896-6273(89)90210-9","article-title":"Multiple isoforms of human microtubule-associated protein tau: Sequences and localization in neurofibrillary tangles of Alzheimer\u2019s disease","volume":"3","author":"Goedert","year":"1989","journal-title":"Neuron"},{"key":"10.3233\/JAD-220125_ref6","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1586\/ern.09.104","article-title":"Mediators of tau phosphorylation in the pathogenesis of Alzheimer\u2019s disease","volume":"9","author":"Hanger","year":"2009","journal-title":"Expert Rev Neurother"},{"key":"10.3233\/JAD-220125_ref7","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1111\/j.1471-4159.1992.tb10039.x","article-title":"Fetal-type phosphorylation of the tau in paired helical filaments","volume":"58","author":"Kanemaru","year":"1992","journal-title":"J Neurochem"},{"key":"10.3233\/JAD-220125_ref8","doi-asserted-by":"crossref","first-page":"24374","DOI":"10.1016\/S0021-9258(20)80536-5","article-title":"Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease","volume":"268","author":"Kopke","year":"1993","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-220125_ref9","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol Med"},{"key":"10.3233\/JAD-220125_ref10","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/NEN.0b013e31825018f7","article-title":"Correlation of Alzheimer disease neuropathologic changes with cognitive status: A review of the literature","volume":"71","author":"Nelson","year":"2012","journal-title":"J Neuropathol Exp Neurol"},{"key":"10.3233\/JAD-220125_ref11","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.brainresbull.2016.08.018","article-title":"Tau and tauopathies","volume":"126","author":"Arendt","year":"2016","journal-title":"Brain Res Bull"},{"key":"10.3233\/JAD-220125_ref12","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1212\/WNL.56.suppl_4.S16","article-title":"Neuropathology of Pick\u2019s disease","volume":"56","author":"Dickson","year":"2001","journal-title":"Neurology"},{"key":"10.3233\/JAD-220125_ref13","doi-asserted-by":"crossref","first-page":"101644","DOI":"10.1016\/j.pneurobio.2019.101644","article-title":"Four-repeat tauopathies","volume":"180","author":"Rosler","year":"2019","journal-title":"Prog Neurobiol"},{"key":"10.3233\/JAD-220125_ref14","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/s41380-018-0342-8","article-title":"Tau PET imaging in neurodegenerative tauopathies-still a challenge","volume":"24","author":"Leuzy","year":"2019","journal-title":"Mol Psychiatry"},{"key":"10.3233\/JAD-220125_ref15","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1007\/s00259-019-04397-2","article-title":"Discovery and preclinical characterization of [(18)F]PI-2620, a next-generation tau PET tracer for the assessment of tau pathology in Alzheimer\u2019s disease and other tauopathies","volume":"46","author":"Kroth","year":"2019","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"10.3233\/JAD-220125_ref16","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1021\/acs.jmedchem.6b00166","article-title":"Discovery of 6-(Fluoro-(18)F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([(18)F]-MK-6240): A positron emission tomography (PET) imaging agent for quantification of neurofibrillary tangles (NFTs)","volume":"59","author":"Walji","year":"2016","journal-title":"J Med Chem"},{"key":"10.3233\/JAD-220125_ref17","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nature23002","article-title":"Cryo-EM structures of tau filaments from Alzheimer\u2019s disease","volume":"547","author":"Fitzpatrick","year":"2017","journal-title":"Nature"},{"key":"10.3233\/JAD-220125_ref18","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41586-018-0454-y","article-title":"Structures of filaments from Pick\u2019s disease reveal a novel tau protein fold","volume":"561","author":"Falcon","year":"2018","journal-title":"Nature"},{"key":"10.3233\/JAD-220125_ref19","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s00401-018-1914-z","article-title":"Tau filaments from multiple cases of sporadic and inherited Alzheimer\u2019s disease adopt a common fold","volume":"136","author":"Falcon","year":"2018","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-220125_ref20","doi-asserted-by":"crossref","first-page":"e43584","DOI":"10.7554\/eLife.43584","article-title":"Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer\u2019s and Pick\u2019s diseases","volume":"8","author":"Zhang","year":"2019","journal-title":"Elife"},{"key":"10.3233\/JAD-220125_ref21","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41586-020-2043-0","article-title":"Novel tau filament fold in corticobasal degeneration","volume":"580","author":"Zhang","year":"2020","journal-title":"Nature"},{"key":"10.3233\/JAD-220125_ref22","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.cell.2020.01.027","article-title":"Posttranslational modifications mediate the structural diversity of tauopathy strains","volume":"180","author":"Arakhamia","year":"2020","journal-title":"Cell"},{"key":"10.3233\/JAD-220125_ref23","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.sbi.2020.05.011","article-title":"Cryo-EM structures of tau filaments","volume":"64","author":"Scheres","year":"2020","journal-title":"Curr Opin Struct Biol"},{"key":"10.3233\/JAD-220125_ref24","doi-asserted-by":"crossref","first-page":"9535","DOI":"10.1073\/pnas.1301175110","article-title":"Brain homogenates from human tauopathies induce tau inclusions in mouse brain","volume":"110","author":"Clavaguera","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-220125_ref25","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.trci.2018.09.005","article-title":"Highly specific and selective anti-pS396-tau antibody C10.2 targets seeding-competent tau","volume":"4","author":"Rosenqvist","year":"2018","journal-title":"Alzheimers Dement (N Y)"},{"key":"10.3233\/JAD-220125_ref26","doi-asserted-by":"crossref","first-page":"108104","DOI":"10.1016\/j.neuropharm.2020.108104","article-title":"Tau immunotherapies: Lessons learned, current status and future considerations","volume":"175","author":"Sandusky-Beltran","year":"2020","journal-title":"Neuropharmacology"},{"key":"10.3233\/JAD-220125_ref27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nature12481","article-title":"Self-propagation of pathogenic protein aggregates in neurodegenerative diseases","volume":"501","author":"Jucker","year":"2013","journal-title":"Nature"},{"key":"10.3233\/JAD-220125_ref28","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/ncb1901","article-title":"Transmission and spreading of tauopathy in transgenic mouse brain","volume":"11","author":"Clavaguera","year":"2009","journal-title":"Nat Cell Biol"},{"key":"10.3233\/JAD-220125_ref29","doi-asserted-by":"crossref","first-page":"E4376","DOI":"10.1073\/pnas.1411649111","article-title":"Proteopathic tau seeding predicts tauopathy in vivo","volume":"111","author":"Holmes","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-220125_ref30","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1523\/JNEUROSCI.3542-15.2016","article-title":"Short fibrils constitute the major species of seed-competent tau in the brains of mice transgenic for human P301S tau","volume":"36","author":"Jackson","year":"2016","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-220125_ref31","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s00401-018-1911-2","article-title":"Epitope determines efficacy of therapeutic anti-tau antibodies in a functional assay with human Alzheimer tau","volume":"136","author":"Courade","year":"2018","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-220125_ref32","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/neup.12189","article-title":"Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program","volume":"35","author":"Beach","year":"2015","journal-title":"Neuropathology"},{"key":"10.3233\/JAD-220125_ref33","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1002\/pro.5560041120","article-title":"How to measure and predict the molar absorption coefficient of a protein","volume":"4","author":"Pace","year":"1995","journal-title":"Protein Sci"},{"key":"10.3233\/JAD-220125_ref34","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1126\/science.7973652","article-title":"Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody","volume":"266","author":"Burton","year":"1994","journal-title":"Science"},{"key":"10.3233\/JAD-220125_ref35","doi-asserted-by":"crossref","first-page":"4219","DOI":"10.1242\/jcs.114.23.4219","article-title":"Dynamic targeting of protein phosphatase 1 within the nuclei of living mammalian cells","volume":"114","author":"Trinkle-Mulcahy","year":"2001","journal-title":"J Cell Sci"},{"key":"10.3233\/JAD-220125_ref36","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1097\/NEN.0b013e318232a379","article-title":"Stages of the pathologic process in Alzheimer disease: Age categories from 1 to 100 years","volume":"70","author":"Braak","year":"2011","journal-title":"J Neuropathol Exp Neurol"},{"key":"10.3233\/JAD-220125_ref37","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00401-006-0127-z","article-title":"Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry","volume":"112","author":"Braak","year":"2006","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-220125_ref38","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"},{"key":"10.3233\/JAD-220125_ref39","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":"10.3233\/JAD-220125_ref40","doi-asserted-by":"crossref","first-page":"eaat8462","DOI":"10.1126\/scitranslmed.aat8462","article-title":"Abeta and tau prion-like activities decline with longevity in the Alzheimer\u2019s disease human brain","volume":"11","author":"Aoyagi","year":"2019","journal-title":"Sci Transl Med"},{"key":"10.3233\/JAD-220125_ref41","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/s41591-020-0938-9","article-title":"Tau molecular diversity contributes to clinical heterogeneity in Alzheimer\u2019s disease","volume":"26","author":"Dujardin","year":"2020","journal-title":"Nat Med"},{"key":"10.3233\/JAD-220125_ref42","doi-asserted-by":"crossref","first-page":"eaau5732","DOI":"10.1126\/scitranslmed.aau5732","article-title":"Prospective longitudinal atrophy in Alzheimer\u2019s disease correlates with the intensity and topography of baseline tau-PET","volume":"12","author":"La Joie","year":"2020","journal-title":"Sci Transl Med"},{"key":"10.3233\/JAD-220125_ref43","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s40336-018-0290-y","article-title":"The development and validation of tau PET tracers: Current status and future directions","volume":"6","author":"Okamura","year":"2018","journal-title":"Clin Transl Imaging"},{"key":"10.3233\/JAD-220125_ref44","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2967\/jnumed.118.208215","article-title":"Brain imaging of Alzheimer dementia patients and elderly controls with (18)F-MK-6240, a PET tracer targeting neurofibrillary tangles","volume":"60","author":"Lohith","year":"2019","journal-title":"J Nucl Med"},{"key":"10.3233\/JAD-220125_ref45","doi-asserted-by":"crossref","first-page":"911","DOI":"10.2967\/jnumed.119.236224","article-title":"Tau PET imaging with (18)F-PI-2620 in patients with Alzheimer disease and healthy controls: A first-in-humans study","volume":"61","author":"Mueller","year":"2020","journal-title":"J Nucl Med"},{"key":"10.3233\/JAD-220125_ref46","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1021\/acschemneuro.9b00578","article-title":"Computational insight into the binding profile of the second-generation PET tracer PI2620 with tau fibrils","volume":"11","author":"Kuang","year":"2020","journal-title":"ACS Chem Neurosci"},{"key":"10.3233\/JAD-220125_ref47","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1007\/s00259-019-04305-8","article-title":"Cross-interaction of tau PET tracers with monoamine oxidase B: Evidence from in silico modelling and in vivo imaging","volume":"46","author":"Murugan","year":"2019","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"10.3233\/JAD-220125_ref48","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/2051-5960-2-14","article-title":"Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism: Relevance to sporadic tauopathies","volume":"2","author":"Dujardin","year":"2014","journal-title":"Acta Neuropathol Commun"},{"key":"10.3233\/JAD-220125_ref49","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.neuron.2011.11.033","article-title":"Propagation of tau pathology in a model of early Alzheimer\u2019s disease","volume":"73","author":"de Calignon","year":"2012","journal-title":"Neuron"},{"key":"10.3233\/JAD-220125_ref50","doi-asserted-by":"crossref","first-page":"e31302","DOI":"10.1371\/journal.pone.0031302","article-title":"Trans-synaptic spread of tau pathology in vivo","volume":"7","author":"Liu","year":"2012","journal-title":"PLoS One"},{"key":"10.3233\/JAD-220125_ref51","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3389\/fnins.2018.00267","article-title":"Synaptic tau seeding precedes tau pathology in human Alzheimer\u2019s disease brain","volume":"12","author":"DeVos","year":"2018","journal-title":"Front Neurosci"},{"key":"10.3233\/JAD-220125_ref52","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00401-015-1507-z","article-title":"Propagation of tau pathology: Hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies","volume":"131","author":"Lewis","year":"2016","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-220125_ref53","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\u2019s disease","volume":"5","author":"Garcia-Sierra","year":"2003","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220125_ref54","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00401-008-0431-x","article-title":"Thiazin red as a neuropathological tool for the rapid diagnosis of Alzheimer\u2019s disease in tissue imprints","volume":"116","author":"Luna-Munoz","year":"2008","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-220125_ref55","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3233\/JAD-181263","article-title":"Phospho-tau changes in the human CA1 during Alzheimer\u2019s disease progression","volume":"69","author":"Regalado-Reyes","year":"2019","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220125_ref56","doi-asserted-by":"crossref","first-page":"417","DOI":"10.3233\/JAD-180173","article-title":"A study of amyloid-beta and phosphotau in plaques and neurons in the hippocampus of Alzheimer\u2019s disease patients","volume":"64","author":"Furcila","year":"2018","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220125_ref57","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.neurobiolaging.2004.09.019","article-title":"Tau truncation during neurofibrillary tangle evolution in Alzheimer\u2019s disease","volume":"26","author":"Guillozet-Bongaarts","year":"2005","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-220125_ref58","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.neuron.2018.04.035","article-title":"Tau kinetics in neurons and the human central nervous system","volume":"98","author":"Sato","year":"2018","journal-title":"Neuron"},{"key":"10.3233\/JAD-220125_ref59","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\u2019s disease","volume":"601","author":"Endoh","year":"1993","journal-title":"Brain Res"},{"key":"10.3233\/JAD-220125_ref60","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0891-0618(01)00096-5","article-title":"Accumulation of C-terminally truncated tau protein associated with vulnerability of the perforant pathway in early stages of neurofibrillary pathology in Alzheimer\u2019s disease","volume":"22","author":"Garcia-Sierra","year":"2001","journal-title":"J Chem Neuroanat"},{"key":"10.3233\/JAD-220125_ref61","first-page":"33","article-title":"The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer\u2019s disease","volume":"9","author":"Flores-Rodriguez","year":"2015","journal-title":"Front Neurosci"},{"key":"10.3233\/JAD-220125_ref62","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00401-015-1503-3","article-title":"Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau","volume":"131","author":"Taniguchi-Watanabe","year":"2016","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-220125_ref63","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40478-020-0884-2","article-title":"Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer\u2019s disease","volume":"8","author":"Roberts","year":"2020","journal-title":"Acta Neuropathol Commun"},{"key":"10.3233\/JAD-220125_ref64","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 eitopes and a new phosphorylation site","volume":"84","author":"Dickson","year":"1992","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-220125_ref65","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fnagi.2019.00121","article-title":"Tau phosphorylation rates measured by mass spectrometry differ in the intracellular brain vs. extracellular cerebrospinal fluid compartments and are differentially affected by Alzheimer\u2019s disease","volume":"11","author":"Barthelemy","year":"2019","journal-title":"Front Aging Neurosci"},{"key":"10.3233\/JAD-220125_ref66","doi-asserted-by":"crossref","first-page":"11406","DOI":"10.1523\/JNEUROSCI.1230-17.2017","article-title":"Pathological tau strains from human brains recapitulate the diversity of tauopathies in nontransgenic mouse brain","volume":"37","author":"Narasimhan","year":"2017","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-220125_ref67","doi-asserted-by":"crossref","first-page":"E8187","DOI":"10.1073\/pnas.1616344113","article-title":"Tau prions from Alzheimer\u2019s disease and chronic traumatic encephalopathy patients propagate in cultured cells","volume":"113","author":"Woerman","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-220125_ref68","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.1074\/jbc.AAC118.002657","article-title":"Distinct differences in prion-like seeding and aggregation between Tau protein variants provide mechanistic insights into tauopathies","volume":"293","author":"Strang","year":"2018","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-220125_ref69","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s40478-019-0686-6","article-title":"Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue","volume":"7","author":"Aguero","year":"2019","journal-title":"Acta Neuropathol Commun"},{"key":"10.3233\/JAD-220125_ref70","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/s00401-005-1031-7","article-title":"Argyrophilic grains are not always argyrophilic\u2013distinction from neurofibrillary tangles of diffuse neurofibrillary tangles with calcification revealed by comparison between Gallyas and Campbell-Switzer methods","volume":"110","author":"Uchihara","year":"2005","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-220125_ref71","doi-asserted-by":"crossref","first-page":"19440","DOI":"10.1074\/jbc.M112.346072","article-title":"Trans-cellular propagation of Tau aggregation by fibrillar species","volume":"287","author":"Kfoury","year":"2012","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-220125_ref72","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":"10.3233\/JAD-220125_ref73","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/alzrt277","article-title":"Identification of structural determinants on tau protein essential for its pathological function: Novel therapeutic target for tau immunotherapy in Alzheimer\u2019s disease","volume":"6","author":"Kontsekova","year":"2014","journal-title":"Alzheimers Res Ther"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-220125","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:06:10Z","timestamp":1777370770000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-220125"}},"subtitle":[],"editor":[{"given":"Colin","family":"Masters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,6,28]]},"references-count":73,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.3233\/jad-220125","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,28]]}}}