{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:27:49Z","timestamp":1760149669457,"version":"build-2065373602"},"reference-count":78,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG066506"],"award-info":[{"award-number":["P30AG066506"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the University of Florida","award":["P30AG066506"],"award-info":[{"award-number":["P30AG066506"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tau proteins within the adult central nervous system (CNS) are found to be abnormally aggregated into heterogeneous filaments in neurodegenerative diseases, termed tauopathies. These tau inclusions are pathological hallmarks of Alzheimer\u2019s disease (AD), Pick\u2019s disease (PiD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP). The neuropathological hallmarks of these diseases burden several cell types within the CNS, and have also been shown to be abundantly phosphorylated. The mechanism(s) by which tau aggregates in the CNS is not fully known, but it is hypothesized that hyperphosphorylated tau may precede and further promote filament formation, leading to the production of these pathological inclusions. In the studies herein, we generated and thoroughly characterized two novel conformation-dependent tau monoclonal antibodies that bind to residues Pro218-Glu222, but are sensitive to denaturing conditions and highly modulated by adjacent downstream phosphorylation sites. These epitopes are present in the neuropathological hallmarks of several tauopathies, including AD, PiD, CBD, and PSP. These novel antibodies will further enable investigation of tau-dependent pathological inclusion formation and enhance our understanding of the phosphorylation signatures within tauopathies with the possibility of new biomarker developments.<\/jats:p>","DOI":"10.3390\/ijms241813676","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T09:46:20Z","timestamp":1693907180000},"page":"13676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel Conformation-Dependent Tau Antibodies Are Modulated by Adjacent Phosphorylation Sites"],"prefix":"10.3390","volume":"24","author":[{"given":"Giavanna","family":"Paterno","sequence":"first","affiliation":[{"name":"Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose","family":"Torrellas","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brach M.","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly-Marie M.","family":"Gorion","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan S.","family":"Quintin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela P.","family":"Hery","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Pathology, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Prokop","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Pathology, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benoit I.","family":"Giasson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1073\/pnas.85.11.4051","article-title":"Cloning and Sequencing of the CDNA Encoding a Core Protein of the Paired Helical Filament of Alzheimer Disease: Identification as the Microtubule-Associated Protein Tau","volume":"85","author":"Goedert","year":"1988","journal-title":"Proc. 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