{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:59:00Z","timestamp":1791410340528,"version":"4.3.3"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["10059436"],"award-info":[{"award-number":["10059436"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["10061100"],"award-info":[{"award-number":["10061100"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["10138075"],"award-info":[{"award-number":["10138075"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Tauopathies are a heterogeneous group of neurodegenerative disorders defined by abnormal aggregation of tau protein. Although cryogenic electron microscopy (cryo\u2010EM) has uncovered disease\u2010specific tau structures, translating these insights into diagnostic tools remains difficult.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We developed a heparin\u2010free, salt\u2010modulated real\u2010time quaking\u2010induced conversion (RT\u2010QuIC) assay using K12 and K11 tau substrates, targeting aggregation\u2010prone regions. This current method improves on previous methodology by minimising the number of required substrates by modulating reaction salt content in order to differentiate yet\u2010undistinguished tauopathy strains. Thioflavin T fluorescence kinetics and attenuated total reflectance Fourier transform infrared spectroscopy (ATR\u2010FTIR) spectroscopy were used to classify tau aggregates from human brain homogenates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>This method differentiated eight tauopathies, including Alzheimer's disease, Pick disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), argyrophilic grain disease (AGD), frontotemporal dementia with parkinsonism associated with chromosome 17 with N279K mutation (FTDP\u201017 N279K), and globular glial tauopathies types II and III. Subclassification of 4R tauopathies was achieved by modulating salt conditions and analyzing aggregation profiles. FTIR confirmed preservation of conformational differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This salt\u2010modulated, heparin\u2010free RT\u2010QuIC platform enables sensitive tauopathy classification based on strain\u2010specific kinetics and structure. It offers a practical tool for diagnostic development, mechanistic studies, and therapeutic screening.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71112","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T10:36:51Z","timestamp":1770979011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Classification of tauopathies from human brain homogenates through salt\u2010modulated tau amplification"],"prefix":"10.1002","volume":"22","author":[{"given":"Alessia","family":"Santambrogio","sequence":"first","affiliation":[{"name":"Centre for Misfolding Diseases Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Michael A.","family":"Metrick","sequence":"additional","affiliation":[{"name":"Centre for Misfolding Diseases Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"},{"name":"Laboratory of Neurological Infections and Immunity Rocky Mountain Laboratories Division of Intramural Research National Institute for Allergy and Infectious Diseases  Hamilton Montana USA"},{"name":"Departments of Pathology and Laboratory Medicine University of California at San Francisco  California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peifeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Centre for Misfolding Diseases Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C. T.","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Centre for Misfolding Diseases Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"},{"name":"Department of Pathology and Laboratory Medicine The University of Pennsylvania  Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardino","family":"Ghetti","sequence":"additional","affiliation":[{"name":"Department of Pathology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis W.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron","family":"Caughey","sequence":"additional","affiliation":[{"name":"Laboratory of Neurological Infections and Immunity Rocky Mountain Laboratories Division of Intramural Research National Institute for Allergy and Infectious Diseases  Hamilton Montana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Vendruscolo","sequence":"additional","affiliation":[{"name":"Centre for Misfolding Diseases Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.1121"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-072116-031153"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03911-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1914-z"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05319-3"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2317-6"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001217"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0710152105"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2294"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004983"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50897"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25446"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0508-2"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.338"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1692-z"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1947-3"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-020-0887-z"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02080-2"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1909322116"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2043-0"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature23002"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90305-5"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-023-01584-z"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.01.027"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43584"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.jnen.0000218446.38158.61"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20782-0"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-05858-7"},{"key":"e_1_2_9_30_1","first-page":"1","article-title":"In vivo hyperphosphorylation of tau is associated with synaptic loss and behavioral abnormalities in the absence of tau seeds","volume":"28","author":"Watamura N","year":"2024","journal-title":"Nat Neurosci"},{"key":"e_1_2_9_31_1","article-title":"Design of tau aggregation inhibitors using iterative machine learning and a polymorph\u2010specific brain\u2010seeded fibril amplification assay","author":"Santambrogio A","year":"2025","journal-title":"bioRxiv"}],"container-title":["Alzheimer's &amp; 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