Amanda E. Denning, Ranjit Ittyerah, Lisa M. Levorse, Niyousha Sadeghpour, Chinmayee Athalye, Eunice Chung, Sadhana Ravikumar, Mengjin Dong, Michael Tran Duong, Yue Li, Ademola Ilesanmi, Lasya P. Sreepada, Philip Sabatini, MaKayla Lowe, Alejandra Bahena, Jamila Zablah, Barbara E. Spencer, Ryohei Watanabe, Boram Kim, Maja Højvang Sørensen, Pulkit Khandelwal, Christopher Brown, Stanislau Hrybouski, Sharon X. Xie, Robin de Flores, John L. Robinson, Theresa Schuck, Daniel T. Ohm, Sanaz Arezoumandan, Sílvia Porta, John A. Detre, Ricardo Insausti, Laura E. M. Wisse, Sandhitsu R. Das, David J. Irwin, Edward B. Lee, David A. Wolk, Paul A. Yushkevich
{"title":"定量组织病理学测量与阿尔茨海默氏症连续症中死前颞叶内侧皮质厚度的关联。","authors":"Amanda E. Denning, Ranjit Ittyerah, Lisa M. Levorse, Niyousha Sadeghpour, Chinmayee Athalye, Eunice Chung, Sadhana Ravikumar, Mengjin Dong, Michael Tran Duong, Yue Li, Ademola Ilesanmi, Lasya P. Sreepada, Philip Sabatini, MaKayla Lowe, Alejandra Bahena, Jamila Zablah, Barbara E. Spencer, Ryohei Watanabe, Boram Kim, Maja Højvang Sørensen, Pulkit Khandelwal, Christopher Brown, Stanislau Hrybouski, Sharon X. Xie, Robin de Flores, John L. Robinson, Theresa Schuck, Daniel T. Ohm, Sanaz Arezoumandan, Sílvia Porta, John A. Detre, Ricardo Insausti, Laura E. M. Wisse, Sandhitsu R. Das, David J. Irwin, Edward B. Lee, David A. Wolk, Paul A. Yushkevich","doi":"10.1007/s00401-024-02789-9","DOIUrl":null,"url":null,"abstract":"<div><p>The medial temporal lobe (MTL) is a hotspot for neuropathology, and measurements of MTL atrophy are often used as a biomarker for cognitive decline associated with neurodegenerative disease. Due to the aggregation of multiple proteinopathies in this region, the specific relationship of MTL atrophy to distinct neuropathologies is not well understood. Here, we develop two quantitative algorithms using deep learning to measure phosphorylated tau (p-tau) and TDP-43 (pTDP-43) pathology, which are both known to accumulate in the MTL and are associated with MTL neurodegeneration. We focus on these pathologies in the context of Alzheimer’s disease (AD) and limbic predominant age-related TDP-43 encephalopathy (LATE) and apply our deep learning algorithms to distinct histology sections, on which MTL subregions were digitally annotated. We demonstrate that both quantitative pathology measures show high agreement with expert visual ratings of pathology and discriminate well between pathology stages. In 140 cases with antemortem MR imaging, we compare the association of semi-quantitative and quantitative postmortem measures of these pathologies in the hippocampus with in vivo structural measures of the MTL and its subregions. We find widespread associations of p-tau pathology with MTL subregional structural measures, whereas pTDP-43 pathology had more limited associations with the hippocampus and entorhinal cortex. Quantitative measurements of p-tau pathology resulted in a significantly better model of antemortem structural measures than semi-quantitative ratings and showed strong associations with cortical thickness and volume. By providing a more granular measure of pathology, the quantitative p-tau measures also showed a significant negative association with structure in a severe AD subgroup where semi-quantitative ratings displayed a ceiling effect. Our findings demonstrate the advantages of using quantitative neuropathology to understand the relationship of pathology to structure, particularly for p-tau, and motivate the use of quantitative pathology measurements in future studies.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371872/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association of quantitative histopathology measurements with antemortem medial temporal lobe cortical thickness in the Alzheimer’s disease continuum\",\"authors\":\"Amanda E. Denning, Ranjit Ittyerah, Lisa M. Levorse, Niyousha Sadeghpour, Chinmayee Athalye, Eunice Chung, Sadhana Ravikumar, Mengjin Dong, Michael Tran Duong, Yue Li, Ademola Ilesanmi, Lasya P. Sreepada, Philip Sabatini, MaKayla Lowe, Alejandra Bahena, Jamila Zablah, Barbara E. Spencer, Ryohei Watanabe, Boram Kim, Maja Højvang Sørensen, Pulkit Khandelwal, Christopher Brown, Stanislau Hrybouski, Sharon X. Xie, Robin de Flores, John L. Robinson, Theresa Schuck, Daniel T. Ohm, Sanaz Arezoumandan, Sílvia Porta, John A. Detre, Ricardo Insausti, Laura E. M. Wisse, Sandhitsu R. Das, David J. Irwin, Edward B. Lee, David A. Wolk, Paul A. Yushkevich\",\"doi\":\"10.1007/s00401-024-02789-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The medial temporal lobe (MTL) is a hotspot for neuropathology, and measurements of MTL atrophy are often used as a biomarker for cognitive decline associated with neurodegenerative disease. Due to the aggregation of multiple proteinopathies in this region, the specific relationship of MTL atrophy to distinct neuropathologies is not well understood. Here, we develop two quantitative algorithms using deep learning to measure phosphorylated tau (p-tau) and TDP-43 (pTDP-43) pathology, which are both known to accumulate in the MTL and are associated with MTL neurodegeneration. We focus on these pathologies in the context of Alzheimer’s disease (AD) and limbic predominant age-related TDP-43 encephalopathy (LATE) and apply our deep learning algorithms to distinct histology sections, on which MTL subregions were digitally annotated. We demonstrate that both quantitative pathology measures show high agreement with expert visual ratings of pathology and discriminate well between pathology stages. In 140 cases with antemortem MR imaging, we compare the association of semi-quantitative and quantitative postmortem measures of these pathologies in the hippocampus with in vivo structural measures of the MTL and its subregions. We find widespread associations of p-tau pathology with MTL subregional structural measures, whereas pTDP-43 pathology had more limited associations with the hippocampus and entorhinal cortex. Quantitative measurements of p-tau pathology resulted in a significantly better model of antemortem structural measures than semi-quantitative ratings and showed strong associations with cortical thickness and volume. By providing a more granular measure of pathology, the quantitative p-tau measures also showed a significant negative association with structure in a severe AD subgroup where semi-quantitative ratings displayed a ceiling effect. 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Association of quantitative histopathology measurements with antemortem medial temporal lobe cortical thickness in the Alzheimer’s disease continuum
The medial temporal lobe (MTL) is a hotspot for neuropathology, and measurements of MTL atrophy are often used as a biomarker for cognitive decline associated with neurodegenerative disease. Due to the aggregation of multiple proteinopathies in this region, the specific relationship of MTL atrophy to distinct neuropathologies is not well understood. Here, we develop two quantitative algorithms using deep learning to measure phosphorylated tau (p-tau) and TDP-43 (pTDP-43) pathology, which are both known to accumulate in the MTL and are associated with MTL neurodegeneration. We focus on these pathologies in the context of Alzheimer’s disease (AD) and limbic predominant age-related TDP-43 encephalopathy (LATE) and apply our deep learning algorithms to distinct histology sections, on which MTL subregions were digitally annotated. We demonstrate that both quantitative pathology measures show high agreement with expert visual ratings of pathology and discriminate well between pathology stages. In 140 cases with antemortem MR imaging, we compare the association of semi-quantitative and quantitative postmortem measures of these pathologies in the hippocampus with in vivo structural measures of the MTL and its subregions. We find widespread associations of p-tau pathology with MTL subregional structural measures, whereas pTDP-43 pathology had more limited associations with the hippocampus and entorhinal cortex. Quantitative measurements of p-tau pathology resulted in a significantly better model of antemortem structural measures than semi-quantitative ratings and showed strong associations with cortical thickness and volume. By providing a more granular measure of pathology, the quantitative p-tau measures also showed a significant negative association with structure in a severe AD subgroup where semi-quantitative ratings displayed a ceiling effect. Our findings demonstrate the advantages of using quantitative neuropathology to understand the relationship of pathology to structure, particularly for p-tau, and motivate the use of quantitative pathology measurements in future 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.