Sujala Ghatamaneni, Courtney Hruska, Ian Shin, Tyler Bruinsma, Nancy Scott, Jeyeon Lee, Ping Fang, Hoon-Ki Min, Christina M. Moloney, Ashley C. Wood, Eleni Constantopoulos, Ross R. Reichard, Christopher G. Schwarz, David T. Jones, Jonathan Graff-Radford, David S. Knopman, Clifford R. Jack Jr., Ronald C. Petersen, Dennis W. Dickson, Melissa E. Murray, Val J. Lowe
{"title":"[18F]MK-6240和[18F]Flortaucipir的高分辨率放射自显像显示相似的神经原纤维缠结结合模式，优先识别中等神经原纤维缠结成熟度","authors":"Sujala Ghatamaneni, Courtney Hruska, Ian Shin, Tyler Bruinsma, Nancy Scott, Jeyeon Lee, Ping Fang, Hoon-Ki Min, Christina M. Moloney, Ashley C. Wood, Eleni Constantopoulos, Ross R. Reichard, Christopher G. Schwarz, David T. Jones, Jonathan Graff-Radford, David S. Knopman, Clifford R. Jack Jr., Ronald C. Petersen, Dennis W. Dickson, Melissa E. Murray, Val J. Lowe","doi":"10.1007/s00401-025-02864-9","DOIUrl":null,"url":null,"abstract":"<div><p>Recent developments in tau positron emission tomography (PET) radiotracers have enhanced the visualization of tau aggregates in Alzheimer’s disease (AD). The maturity level of neurofibrillary tangles can affect its recognition by biomarkers. Early detection of tau aggregates regarding tangle pathology is of interest in early diagnosis and comparison of tau radiotracers in this aspect is important. This study focused on head to head pathologic comparison of [<sup>18</sup>F]MK-6240 and [<sup>18</sup>F]Flortaucipir postmortem binding as seen on high resolution autoradiography as compared to CP-13 (early tangle maturity) and PHF-1 (middling tangle maturity) immunohistochemistry (IHC) to evaluate the tangle maturity pathology specificity of binding for tau aggregates in AD, atypical AD and non-AD tauopathies. Analyses were performed on serial 5 μm formalin-fixed paraffin-embedded human brain sections acquired from the Mayo Clinic brain bank. Visual assessment of colocalization with IHC as well as quantitative analyses were used. Evaluation of the tracers’ off-target binding profiles were performed. Both tracers had similar binding properties for tau aggregates with preference to middling tangle maturity as shown by comparison to immunohistochemical distributions. Both the tracers showed strong binding to AD tau aggregates and no or minimal binding to non-AD tauopathies which corroborates with other studies.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"149 1","pages":""},"PeriodicalIF":9.3000,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-025-02864-9.pdf","citationCount":"0","resultStr":"{\"title\":\"High resolution autoradiography of [18F]MK-6240 and [18F]Flortaucipir shows similar neurofibrillary tangle binding patterns preferentially recognizing middling neurofibrillary tangle maturity\",\"authors\":\"Sujala Ghatamaneni, Courtney Hruska, Ian Shin, Tyler Bruinsma, Nancy Scott, Jeyeon Lee, Ping Fang, Hoon-Ki Min, Christina M. Moloney, Ashley C. Wood, Eleni Constantopoulos, Ross R. Reichard, Christopher G. Schwarz, David T. Jones, Jonathan Graff-Radford, David S. Knopman, Clifford R. Jack Jr., Ronald C. Petersen, Dennis W. Dickson, Melissa E. Murray, Val J. Lowe\",\"doi\":\"10.1007/s00401-025-02864-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Recent developments in tau positron emission tomography (PET) radiotracers have enhanced the visualization of tau aggregates in Alzheimer’s disease (AD). The maturity level of neurofibrillary tangles can affect its recognition by biomarkers. Early detection of tau aggregates regarding tangle pathology is of interest in early diagnosis and comparison of tau radiotracers in this aspect is important. This study focused on head to head pathologic comparison of [<sup>18</sup>F]MK-6240 and [<sup>18</sup>F]Flortaucipir postmortem binding as seen on high resolution autoradiography as compared to CP-13 (early tangle maturity) and PHF-1 (middling tangle maturity) immunohistochemistry (IHC) to evaluate the tangle maturity pathology specificity of binding for tau aggregates in AD, atypical AD and non-AD tauopathies. Analyses were performed on serial 5 μm formalin-fixed paraffin-embedded human brain sections acquired from the Mayo Clinic brain bank. Visual assessment of colocalization with IHC as well as quantitative analyses were used. Evaluation of the tracers’ off-target binding profiles were performed. Both tracers had similar binding properties for tau aggregates with preference to middling tangle maturity as shown by comparison to immunohistochemical distributions. Both the tracers showed strong binding to AD tau aggregates and no or minimal binding to non-AD tauopathies which corroborates with other studies.</p></div>\",\"PeriodicalId\":7012,\"journal\":{\"name\":\"Acta Neuropathologica\",\"volume\":\"149 1\",\"pages\":\"\"},\"PeriodicalIF\":9.3000,\"publicationDate\":\"2025-03-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://link.springer.com/content/pdf/10.1007/s00401-025-02864-9.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Neuropathologica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s00401-025-02864-9\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Neuropathologica","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s00401-025-02864-9","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
High resolution autoradiography of [18F]MK-6240 and [18F]Flortaucipir shows similar neurofibrillary tangle binding patterns preferentially recognizing middling neurofibrillary tangle maturity
Recent developments in tau positron emission tomography (PET) radiotracers have enhanced the visualization of tau aggregates in Alzheimer’s disease (AD). The maturity level of neurofibrillary tangles can affect its recognition by biomarkers. Early detection of tau aggregates regarding tangle pathology is of interest in early diagnosis and comparison of tau radiotracers in this aspect is important. This study focused on head to head pathologic comparison of [18F]MK-6240 and [18F]Flortaucipir postmortem binding as seen on high resolution autoradiography as compared to CP-13 (early tangle maturity) and PHF-1 (middling tangle maturity) immunohistochemistry (IHC) to evaluate the tangle maturity pathology specificity of binding for tau aggregates in AD, atypical AD and non-AD tauopathies. Analyses were performed on serial 5 μm formalin-fixed paraffin-embedded human brain sections acquired from the Mayo Clinic brain bank. Visual assessment of colocalization with IHC as well as quantitative analyses were used. Evaluation of the tracers’ off-target binding profiles were performed. Both tracers had similar binding properties for tau aggregates with preference to middling tangle maturity as shown by comparison to immunohistochemical distributions. Both the tracers showed strong binding to AD tau aggregates and no or minimal binding to non-AD tauopathies which corroborates with other studies.
期刊介绍：
Acta Neuropathologica publishes top-quality papers on the pathology of neurological diseases and experimental studies on molecular and cellular mechanisms using in vitro and in vivo models, ideally validated by analysis of human tissues. The journal accepts Original Papers, Review Articles, Case Reports, and Scientific Correspondence (Letters). Manuscripts must adhere to ethical standards, including review by appropriate ethics committees for human studies and compliance with principles of laboratory animal care for animal experiments. Failure to comply may result in rejection of the manuscript, and authors are responsible for ensuring accuracy and adherence to these requirements.
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