{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T07:27:09Z","timestamp":1793863629669,"version":"4.6.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"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","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016608","name":"Rainwater Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Flortaucipir PET imaging has significantly advanced our ability to visualize tau pathology in vivo. However, off-target Flortaucipir signal remains a considerable challenge for interpreting of imaging results, particularly in non-Alzheimer's tauopathies and non-tau pathologies. To better understand this off-target signal, we used an innovative voxel-to-voxel correlation approach, analyzing thousands of histology-Flortaucipir pairs from individual cases. This allowed us to quantitatively assess the relationship between Flortaucipir PET signal and three key biological factors: histological tau burden (CP-13 phospho-tau), ferric iron (Perls\u2019 Prussian blue), and monoamine oxidase B (MAO-B). Our study included individuals with Alzheimer's disease (AD), various non-AD tauopathies, and a case of FTLD-TDP-43 type A. In AD, Flortaucipir signal showed a significant but moderate correlation with histological tau pathology, suggesting that while tau is a major contributor, other biological factors also influence Flortaucipir binding in AD. Conversely, in non-AD tauopathies and FTLD-TDP-43, correlations between Flortaucipir signal and tau pathology were weak or negligible. Instead, Flortaucipir signal correlated more strongly with ferric iron and MAO-B. However, these factors did not fully explain all the off-target signals, implying other unknown contributors are likely involved. These findings underscore the complexity of interpreting Flortaucipir PET scans. A thorough understanding of off-target binding mechanisms is crucial for improving the diagnostic accuracy of Flortaucipir PET and its specificity.<\/jats:p>","DOI":"10.1007\/s00401-026-02983-x","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T11:02:32Z","timestamp":1772017352000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Disentangling on and off-target binding in flortaucipir PET: a voxel-to-voxel P-tau, ferric iron, and MAO-B histology-to-flortaucipir PET comparison"],"prefix":"10.1007","volume":"151","author":[{"given":"Yuheng","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"La Joie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe L.","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganna","family":"Blazhenets","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucile","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Spina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Seeley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Heinsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Ushizima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duygu","family":"Tosun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil D.","family":"Rabinovici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea T.","family":"Grinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"2983_CR1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-023-02672-z","volume":"147","author":"C Aguero","year":"2024","unstructured":"Aguero C, Dhaynaut M, Amaral AC, Moon SH, Neelamegam R, Scapellato M et al (2024) Head-to-head comparison of [(18)F]-flortaucipir, [(18)F]-MK-6240 and [(18)F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases. Acta Neuropathol 147:25. https:\/\/doi.org\/10.1007\/s00401-023-02672-z","journal-title":"Acta Neuropathol"},{"key":"2983_CR2","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.2967\/jnumed.118.224113","volume":"60","author":"SL Baker","year":"2019","unstructured":"Baker SL, Harrison TM, Maass A, La Joie R, Jagust WJ (2019) Effect of off-target binding on (18)F-flortaucipir variability in healthy controls across the life span. J Nucl Med 60:1444\u20131451. https:\/\/doi.org\/10.2967\/jnumed.118.224113","journal-title":"J Nucl Med"},{"key":"2983_CR3","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1212\/WNL.0000000000002892","volume":"87","author":"H Cho","year":"2016","unstructured":"Cho H, Choi JY, Hwang MS, Lee JH, Kim YJ, Lee HM et al (2016) Tau PET in Alzheimer disease and mild cognitive impairment. Neurology 87:375\u2013383. https:\/\/doi.org\/10.1212\/WNL.0000000000002892","journal-title":"Neurology"},{"key":"2983_CR4","doi-asserted-by":"publisher","first-page":"117","DOI":"10.2967\/jnumed.117.195248","volume":"59","author":"JY Choi","year":"2018","unstructured":"Choi JY, Cho H, Ahn SJ, Lee JH, Ryu YH, Lee MS et al (2018) Off-target (18)F-AV-1451 binding in the basal ganglia correlates with age-related iron accumulation. J Nucl Med 59:117\u2013120. https:\/\/doi.org\/10.2967\/jnumed.117.195248","journal-title":"J Nucl Med"},{"key":"2983_CR5","doi-asserted-by":"publisher","first-page":"3839","DOI":"10.1021\/acschemneuro.9b00326","volume":"10","author":"LR Drake","year":"2019","unstructured":"Drake LR, Pham JM, Desmond TJ, Mossine AV, Lee SJ, Kilbourn MR et al (2019) Identification of AV-1451 as a weak, nonselective inhibitor of monoamine oxidase. ACS Chem Neurosci 10:3839\u20133846. https:\/\/doi.org\/10.1021\/acschemneuro.9b00326","journal-title":"ACS Chem Neurosci"},{"key":"2983_CR6","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1007\/s11307-017-1143-1","volume":"20","author":"AK Hansen","year":"2018","unstructured":"Hansen AK, Brooks DJ, Borghammer P (2018) MAO-B inhibitors do not block in vivo flortaucipir([(18)F]-AV-1451) binding. Mol Imaging Biol 20:356\u2013360. https:\/\/doi.org\/10.1007\/s11307-017-1143-1","journal-title":"Mol Imaging Biol"},{"key":"2983_CR7","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-024-02712-2","volume":"147","author":"M Jaisa-Aad","year":"2024","unstructured":"Jaisa-Aad M, Munoz-Castro C, Healey MA, Hyman BT, Serrano-Pozo A (2024) Characterization of monoamine oxidase-B (MAO-B) as a biomarker of reactive astrogliosis in Alzheimer\u2019s disease and related dementias. Acta Neuropathol 147:66. https:\/\/doi.org\/10.1007\/s00401-024-02712-2","journal-title":"Acta Neuropathol"},{"key":"2983_CR8","doi-asserted-by":"publisher","DOI":"10.3390\/ph14020110","author":"C Jie","year":"2021","unstructured":"Jie C, Treyer V, Schibli R, Mu L (2021) Tauvid\u2122: the first FDA-approved PET tracer for imaging tau pathology in Alzheimer\u2019s disease. Pharmaceuticals (Basel). https:\/\/doi.org\/10.3390\/ph14020110","journal-title":"Pharmaceuticals (Basel)"},{"key":"2983_CR9","doi-asserted-by":"publisher","first-page":"931","DOI":"10.2967\/jnumed.121.262685","volume":"63","author":"KA Josephs","year":"2022","unstructured":"Josephs KA, Tosakulwong N, Weigand SD, Buciuc M, Lowe VJ, Dickson DW et al (2022) Relationship between (18)F-flortaucipir uptake and histologic lesion types in 4-repeat tauopathies. J Nucl Med 63:931\u2013935. https:\/\/doi.org\/10.2967\/jnumed.121.262685","journal-title":"J Nucl Med"},{"key":"2983_CR10","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/B978-0-12-802395-2.00025-0","volume":"145","author":"GG Kovacs","year":"2017","unstructured":"Kovacs GG (2017) Tauopathies. Handb Clin Neurol 145:355\u2013368. https:\/\/doi.org\/10.1016\/B978-0-12-802395-2.00025-0","journal-title":"Handb Clin Neurol"},{"key":"2983_CR11","doi-asserted-by":"publisher","first-page":"3614","DOI":"10.1111\/ejn.16362","volume":"60","author":"J Langley","year":"2024","unstructured":"Langley J, Bennett IJ, Hu XP, Alzheimer\u2019s Disease Neuroimaging I (2024) Examining iron-related off-target binding effects of (18)F-AV1451 PET in the cortex of Abeta+ individuals. Eur J Neurosci 60:3614\u20133628. https:\/\/doi.org\/10.1111\/ejn.16362","journal-title":"Eur J Neurosci"},{"key":"2983_CR12","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.parkreldis.2017.09.020","volume":"45","author":"SH Lee","year":"2017","unstructured":"Lee SH, Lyoo CH, Ahn SJ, Rinne JO, Lee MS (2017) Brain regional iron contents in progressive supranuclear palsy. Parkinsonism Relat Disord 45:28\u201332. https:\/\/doi.org\/10.1016\/j.parkreldis.2017.09.020","journal-title":"Parkinsonism Relat Disord"},{"key":"2983_CR13","doi-asserted-by":"publisher","first-page":"632","DOI":"10.3389\/fnins.2018.00632","volume":"12","author":"JL Liu","year":"2018","unstructured":"Liu JL, Fan YG, Yang ZS, Wang ZY, Guo C (2018) Iron and Alzheimer\u2019s disease: from pathogenesis to therapeutic implications. Front Neurosci 12:632. https:\/\/doi.org\/10.3389\/fnins.2018.00632","journal-title":"Front Neurosci"},{"key":"2983_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2022.119396","volume":"259","author":"FJ Lopez-Gonzalez","year":"2022","unstructured":"Lopez-Gonzalez FJ, Costoya-Sanchez A, Paredes-Pacheco J, Moscoso A, Silva-Rodriguez J, Aguiar P et al (2022) Impact of spill-in counts from off-target regions on [(18)F]Flortaucipir PET quantification. Neuroimage 259:119396. https:\/\/doi.org\/10.1016\/j.neuroimage.2022.119396","journal-title":"Neuroimage"},{"key":"2983_CR15","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s40478-016-0315-6","volume":"4","author":"VJ Lowe","year":"2016","unstructured":"Lowe VJ, Curran G, Fang P, Liesinger AM, Josephs KA, Parisi JE et al (2016) An autoradiographic evaluation of AV-1451 Tau PET in dementia. Acta Neuropathol Commun 4:58. https:\/\/doi.org\/10.1186\/s40478-016-0315-6","journal-title":"Acta Neuropathol Commun"},{"key":"2983_CR16","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.jalz.2019.09.079","volume":"16","author":"VJ Lowe","year":"2020","unstructured":"Lowe VJ, Lundt ES, Albertson SM, Min HK, Fang P, Przybelski SA et al (2020) Tau-positron emission tomography correlates with neuropathology findings. Alzheimers Dement 16:561\u2013571. https:\/\/doi.org\/10.1016\/j.jalz.2019.09.079","journal-title":"Alzheimers Dement"},{"key":"2983_CR17","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1136\/jnnp-2017-316409","volume":"89","author":"SJ Makaretz","year":"2018","unstructured":"Makaretz SJ, Quimby M, Collins J, Makris N, McGinnis S, Schultz A et al (2018) Flortaucipir tau PET imaging in semantic variant primary progressive aphasia. J Neurol Neurosurg Psychiatry 89:1024\u20131031. https:\/\/doi.org\/10.1136\/jnnp-2017-316409","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2983_CR18","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1001\/jamaneurol.2019.4509","volume":"77","author":"WG Mantyh","year":"2020","unstructured":"Mantyh WG, Spina S, Lee A, Iaccarino L, Soleimani-Meigooni D, Tsoy E et al (2020) Tau positron emission tomographic findings in a former US football player with pathologically confirmed chronic traumatic encephalopathy. JAMA Neurol 77:517\u2013521. https:\/\/doi.org\/10.1001\/jamaneurol.2019.4509","journal-title":"JAMA Neurol"},{"key":"2983_CR19","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1002\/ana.24844","volume":"81","author":"M Marquie","year":"2017","unstructured":"Marquie M, Normandin MD, Meltzer AC, Siao Tick Chong M, Andrea NV, Anton-Fernandez A et al (2017) Pathological correlations of [F-18]-AV-1451 imaging in non-alzheimer tauopathies. Ann Neurol 81:117\u2013128. https:\/\/doi.org\/10.1002\/ana.24844","journal-title":"Ann Neurol"},{"key":"2983_CR20","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1002\/ana.24517","volume":"78","author":"M Marquie","year":"2015","unstructured":"Marquie M, Normandin MD, Vanderburg CR, Costantino IM, Bien EA, Rycyna LG et al (2015) Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. Ann Neurol 78:787\u2013800. https:\/\/doi.org\/10.1002\/ana.24517","journal-title":"Ann Neurol"},{"key":"2983_CR21","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s40478-017-0482-0","volume":"5","author":"M Marquie","year":"2017","unstructured":"Marquie M, Verwer EE, Meltzer AC, Kim SJW, Aguero C, Gonzalez J et al (2017) Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson\u2019s case. Acta Neuropathol Commun 5:75. https:\/\/doi.org\/10.1186\/s40478-017-0482-0","journal-title":"Acta Neuropathol Commun"},{"key":"2983_CR22","doi-asserted-by":"crossref","unstructured":"Mertens T, Kautz J, Reeth FV (2007) Exposure fusion. In: 15th pacific conference on computer graphics and applications (PG'07), City, pp 382\u2013390","DOI":"10.1109\/PG.2007.17"},{"key":"2983_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-011-0910-3","volume":"123","author":"TJ Montine","year":"2012","unstructured":"Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW et al (2012) National Institute on Aging-Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease: a practical approach. Acta Neuropathol 123:1\u201311. https:\/\/doi.org\/10.1007\/s00401-011-0910-3","journal-title":"Acta Neuropathol"},{"key":"2983_CR24","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13195-017-0253-y","volume":"9","author":"KP Ng","year":"2017","unstructured":"Ng KP, Pascoal TA, Mathotaarachchi S, Therriault J, Kang MS, Shin M et al (2017) Monoamine oxidase B inhibitor, selegiline, reduces (18)F-THK5351 uptake in the human brain. Alzheimers Res Ther 9:25. https:\/\/doi.org\/10.1186\/s13195-017-0253-y","journal-title":"Alzheimers Res Ther"},{"key":"2983_CR25","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1001\/jama.2018.12917","volume":"320","author":"R Ossenkoppele","year":"2018","unstructured":"Ossenkoppele R, Rabinovici GD, Smith R, Cho H, Scholl M, Strandberg O et al (2018) Discriminative accuracy of [18F]flortaucipir positron emission tomography for Alzheimer disease vs other neurodegenerative disorders. JAMA 320:1151\u20131162. https:\/\/doi.org\/10.1001\/jama.2018.12917","journal-title":"JAMA"},{"key":"2983_CR26","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1093\/brain\/aww340","volume":"140","author":"L Passamonti","year":"2017","unstructured":"Passamonti L, Vazquez Rodriguez P, Hong YT, Allinson KS, Williamson D, Borchert RJ et al (2017) 18F-AV-1451 positron emission tomography in Alzheimer\u2019s disease and progressive supranuclear palsy. Brain 140:781\u2013791. https:\/\/doi.org\/10.1093\/brain\/aww340","journal-title":"Brain"},{"key":"2983_CR27","doi-asserted-by":"publisher","DOI":"10.1186\/s13550-020-00653-x","volume":"10","author":"MJ Pontecorvo","year":"2020","unstructured":"Pontecorvo MJ, Keene CD, Beach TG, Montine TJ, Arora AK, Devous MD Sr. et al (2020) Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer\u2019s disease pathology: a clinicopathological study. EJNMMI Res 10:65. https:\/\/doi.org\/10.1186\/s13550-020-00653-x","journal-title":"EJNMMI Res"},{"key":"2983_CR28","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jtemb.2013.08.001","volume":"28","author":"P Ramos","year":"2014","unstructured":"Ramos P, Santos A, Pinto NR, Mendes R, Magalhaes T, Almeida A (2014) Iron levels in the human brain: a post-mortem study of anatomical region differences and age-related changes. J Trace Elem Med Biol 28:13\u201317. https:\/\/doi.org\/10.1016\/j.jtemb.2013.08.001","journal-title":"J Trace Elem Med Biol"},{"key":"2983_CR29","doi-asserted-by":"publisher","first-page":"2282","DOI":"10.1002\/mds.29613","volume":"38","author":"R Satoh","year":"2023","unstructured":"Satoh R, Weigand SD, Pham NTT, Ali F, Arani A, Senjem ML et al (2023) Magnetic susceptibility in progressive supranuclear palsy variants, Parkinson\u2019s disease, and corticobasal syndrome. Mov Disord 38:2282\u20132290. https:\/\/doi.org\/10.1002\/mds.29613","journal-title":"Mov Disord"},{"key":"2983_CR30","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.sbi.2020.05.011","volume":"64","author":"SH Scheres","year":"2020","unstructured":"Scheres SH, Zhang W, Falcon B, Goedert M (2020) Cryo-EM structures of tau filaments. Curr Opin Struct Biol 64:17\u201325. https:\/\/doi.org\/10.1016\/j.sbi.2020.05.011","journal-title":"Curr Opin Struct Biol"},{"key":"2983_CR31","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.neuron.2016.01.028","volume":"89","author":"M Scholl","year":"2016","unstructured":"Scholl M, Lockhart SN, Schonhaut DR, O\u2019Neil JP, Janabi M, Ossenkoppele R et al (2016) PET imaging of tau deposition in the aging human brain. Neuron 89:971\u2013982. https:\/\/doi.org\/10.1016\/j.neuron.2016.01.028","journal-title":"Neuron"},{"key":"2983_CR32","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1002\/ana.25060","volume":"18","author":"DR Schonhaut","year":"2017","unstructured":"Schonhaut DR, McMillan CT, Spina S, Dickerson BC, Siderowf A, Devous MD Sr. et al (2017) (18) F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: a multicenter study. Ann Neurol 18:622\u2013634. https:\/\/doi.org\/10.1002\/ana.25060","journal-title":"Ann Neurol"},{"key":"2983_CR33","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1093\/brain\/aww163","volume":"139","author":"R Smith","year":"2016","unstructured":"Smith R, Puschmann A, Scholl M, Ohlsson T, van Swieten J, Honer M et al (2016) 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers. Brain 139:2372\u20132379. https:\/\/doi.org\/10.1093\/brain\/aww163","journal-title":"Brain"},{"key":"2983_CR34","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1001\/jamaneurol.2018.3692","volume":"76","author":"R Smith","year":"2019","unstructured":"Smith R, Wibom M, Pawlik D, Englund E, Hansson O (2019) Correlation of in vivo [18F]flortaucipir with postmortem Alzheimer disease tau pathology. JAMA Neurol 76:310\u2013317. https:\/\/doi.org\/10.1001\/jamaneurol.2018.3692","journal-title":"JAMA Neurol"},{"key":"2983_CR35","doi-asserted-by":"publisher","first-page":"3477","DOI":"10.1093\/brain\/awaa276","volume":"143","author":"DN Soleimani-Meigooni","year":"2020","unstructured":"Soleimani-Meigooni DN, Iaccarino L, La Joie R, Baker S, Bourakova V, Boxer AL et al (2020) 18F-flortaucipir PET to autopsy comparisons in Alzheimer\u2019s disease and other neurodegenerative diseases. Brain 143:3477\u20133494. https:\/\/doi.org\/10.1093\/brain\/awaa276","journal-title":"Brain"},{"key":"2983_CR36","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12133","volume":"12","author":"I Sonni","year":"2020","unstructured":"Sonni I, Lesman Segev OH, Baker SL, Iaccarino L, Korman D, Rabinovici GD et al (2020) Evaluation of a visual interpretation method for tau-PET with (18)F-flortaucipir. Alzheimers Dement (Amst) 12:e12133. https:\/\/doi.org\/10.1002\/dad2.12133","journal-title":"Alzheimers Dement (Amst)"},{"key":"2983_CR37","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsisyn.2025.100627","volume":"11","author":"A Sonoda","year":"2025","unstructured":"Sonoda A, Nihei M, Shinkawa N, Kakizaki E, Yukawa N (2025) Perls\u2019 Prussian blue staining and chemistry of Prussian blue and Turnbull blue. Forens Sci Int: Synergy 11:100627. https:\/\/doi.org\/10.1016\/j.fsisyn.2025.100627","journal-title":"Forens Sci Int: Synergy"},{"key":"2983_CR38","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s13195-019-0470-7","volume":"11","author":"RM Tsai","year":"2019","unstructured":"Tsai RM, Bejanin A, Lesman-Segev O, LaJoie R, Visani A, Bourakova V et al (2019) (18)F-flortaucipir (AV-1451) tau PET in frontotemporal dementia syndromes. Alzheimers Res Ther 11:13. https:\/\/doi.org\/10.1186\/s13195-019-0470-7","journal-title":"Alzheimers Res Ther"},{"key":"2983_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.118790","volume":"248","author":"D Ushizima","year":"2022","unstructured":"Ushizima D, Chen Y, Alegro M, Ovando D, Eser R, Lee W et al (2022) Deep learning for Alzheimer\u2019s disease: mapping large-scale histological tau protein for neuroimaging biomarker validation. Neuroimage 248:118790. https:\/\/doi.org\/10.1016\/j.neuroimage.2021.118790","journal-title":"Neuroimage"},{"key":"2983_CR40","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1002\/mds.27271","volume":"33","author":"C Vermeiren","year":"2018","unstructured":"Vermeiren C, Motte P, Viot D, Mairet-Coello G, Courade JP, Citron M et al (2018) The tau positron-emission tomography tracer AV-1451 binds with similar affinities to tau fibrils and monoamine oxidases. Mov Disord 33:273\u2013281. https:\/\/doi.org\/10.1002\/mds.27271","journal-title":"Mov Disord"},{"key":"2983_CR41","doi-asserted-by":"publisher","first-page":"3797","DOI":"10.1007\/s00259-022-05822-9","volume":"49","author":"JP Wright","year":"2022","unstructured":"Wright JP, Goodman JR, Lin YG, Lieberman BP, Clemens J, Gomez LF et al (2022) Monoamine oxidase binding not expected to significantly affect [(18)F]flortaucipir PET interpretation. Eur J Nucl Med Mol Imaging 49:3797\u20133808. https:\/\/doi.org\/10.1007\/s00259-022-05822-9","journal-title":"Eur J Nucl Med Mol Imaging"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-026-02983-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-026-02983-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-026-02983-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T11:02:36Z","timestamp":1772017356000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00401-026-02983-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["2983"],"URL":"https:\/\/doi.org\/10.1007\/s00401-026-02983-x","relation":{},"ISSN":["1432-0533"],"issn-type":[{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]},"assertion":[{"value":"3 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 December 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}],"article-number":"21"}}