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Article (Scientific journals)
Brain connectomics: time for a molecular imaging perspective?
Sala, Arianna; Lizarraga, Aldana; Caminiti, Silvia Paola et al.
2023 • In Trends in Cognitive Sciences
Peer Reviewed verified by ORBi
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https://hdl.handle.net/2268/299349
DOI
10.1016/j.tics.2022.11.015
PubMed
36621368
 

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Keywords :
PET; connectivity; electroencephalography; magnetic resonance imaging; networks; positron emission tomography; Brain connectivity; Brain functions; Connectomics; Electrophysiological techniques; Functional magnetic resonance imaging; Hemodynamic signals; Network; Neural activity; Neuropsychology and Physiological Psychology; Experimental and Cognitive Psychology; Cognitive Neuroscience
Abstract :
[en] In the past two decades brain connectomics has evolved into a major concept in neuroscience. However, the current perspective on brain connectivity and how it underpins brain function relies mainly on the hemodynamic signal of functional magnetic resonance imaging (MRI). Molecular imaging provides unique information inaccessible to MRI-based and electrophysiological techniques. Thus, positron emission tomography (PET) has been successfully applied to measure neural activity, neurotransmission, and proteinopathies in normal and pathological cognition. Here, we position molecular imaging within the brain connectivity framework from the perspective of timeliness, validity, reproducibility, and resolution. We encourage the neuroscientific community to take an integrative approach whereby MRI-based, electrophysiological techniques, and molecular imaging contribute to our understanding of the brain connectome.
Disciplines :
Neurosciences & behavior
Author, co-author :
Sala, Arianna  ;  Université de Liège - ULiège > GIGA > GIGA Consciousness - Coma Science Group ; TUM - Technische Universität München [DE]
Lizarraga, Aldana;  Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, School of Medicine, 81675 Munich, Germany
Caminiti, Silvia Paola;  Vita-Salute San Raffaele University, 20132 Milan, Italy, In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, 20132 Milan, Italy
Calhoun, Vince D;  Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, and Emory University, Atlanta, GA 30303, USA
Eickhoff, Simon B;  Institute of Neuroscience and Medicine, Brain, and Behaviour (INM-7), Research Centre Jülich, 52428 Jülich, Germany, Institute of Systems Neuroscience, Medical Faculty, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany
Habeck, Christian;  Cognitive Neuroscience Division, Department of Neurology, Columbia University, New York, NY 10032, USA
Jamadar, Sharna D;  Turner Institute for Brain and Mental Health, Monash University, 3800 Melbourne, Australia, Monash Biomedical Imaging, Monash University, 3800 Melbourne, Australia
Perani, Daniela;  Vita-Salute San Raffaele University, 20132 Milan, Italy, In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, 20132 Milan, Italy, Nuclear Medicine Unit, San Raffaele Hospital, 20132 Milan, Italy
Pereira, Joana B;  Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 14152 Stockholm, Sweden, Memory Research Unit, Department of Clinical Sciences, Malmö Lund University, 20502 Lund, Sweden
Veronese, Mattia;  Department of Neuroimaging, King's College London, London SE5 8AF, UK, Department of Information Engineering, University of Padua, 35131 Padua, Italy
Yakushev, Igor;  Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, School of Medicine, 81675 Munich, Germany. Electronic address: igor.yakushev@tum.de
Language :
English
Title :
Brain connectomics: time for a molecular imaging perspective?
Publication date :
06 January 2023
Journal title :
Trends in Cognitive Sciences
ISSN :
1364-6613
eISSN :
1879-307X
Publisher :
Elsevier Ltd, England
Peer reviewed :
Peer Reviewed verified by ORBi
Additional URL :
https://api.elsevier.com/content/article/PII:S136466132200300X?httpAccept=text/xml
Funding text :
A.S. is funded by the Belgian National Fund for Scientific Research [grant 40001328, Chargée de Recherches Fonds de la Recherche Scientifique (FRS)/Fonds National de la Recherche Scientifique (FNRS)/Université de Liège/Coma Science Group GIGA]. V.D.C. is supported by the National Institutes of Health (NIH; R01MH118695) and the National Science Foundation (21124550). S.B.E. is funded by the EU Horizon 2020 Research and Innovation Program [grant agreements 945539 (HBP SGA3) and 826421 (VBC)] and the Deutsche Forschungsgemeinschaft (SFB 1451, IRTG 2150). M.V. is funded by the Ministero dell'istruzione, dell'università e della ricerca (MIUR) under the initiative 'Departments of Excellence' (Law 232/2016), by a Wellcome Trust Digital Award (215747/Z/19/Z), and by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King's College London. J.B.P. is funded by the Swedish Research Council. S.D.J. is supported by a National Health and Medical Research Council of Australia Fellowship (APP1174164). We thank Giulia Carli and Hubertus Hautzel for providing data for Table S1. We also thank Rick Adams, Marilyn Albert, Ricardo Allegri, Silvia Alonso-Lana, Andrea Arighi, Murat Bilgel, Alexa Pichet Binette, Gérard N. Bischof, Mercè Boada, Ilaria Bonoldi, Chris Brown, Min S. Byun, Stephen F. Carter, Massimo Castellani, Jaime J. Castrellon, Jiří Cerman, Kewei Chen, Gaël Chetelat, Andrea Chincarini, Patricio Chrem, Lyduine Collij, Anka Cuderman, Tarik Dahoun, Michael D. Devous, Ramon Diaz-Arrastia, Paul Donaghy, Rachelle Doody, Massimo Dottorini, Carole Dufouil, Germán Falasco, Carles Falcon, Sara B. Festini, Christopher Fowle, Peter Fox, Crystal Franklin, Jurgen Fripp, Giovanni Frisoni, Giorgio Fumagalli, Valentin Fuster on behalf of the Progression of Early Subclinical Atherosclerosis (PESA) Study Team, Daniela Galimberti, Melanie Ganz, Valentina Garibotto, Juan D. Gispert, Karl Herholz, Rainer Hinz, Russ Hornbeck, Oliver Howes, Lauren Hudswell, Jordi Huguet, Leonardo Iaccarino, Janne Isojärvi, Takeshi Iwatsubo, Sameer Jahuar, Hyemin Jang, Peter S. Jensen, Sterling Johnson, Kristen Kennedy, David S. Knopman, Pamela LaMontagne, Susan Landau, Jessica Langbaum, Rachael Lawson, Dong Y. Lee, Francisco Lopera, Hanzhang Lu, Emma Luckett, Maura Malpetti, Marta Marquié, Robert McCutcheon, Ian M. McDonough, Richard McIntyre, Patrizia Mecocci, Lefkos Middleton, Yasuhiko Mikari, Valeria Mondelli, Silvia Morbelli, Alice Murphy, Maria A. Nettis, Flavio Nobili, Martin Nørgaard, Matthew Nour, Lauri Nummenmaa, John O'Brien, Grégory Operto, Rik Ossenkoppele, Carmine Pariante, Denise Park, Matej Perovnik, Michela Pievani, Thad Polk, Luca Presotto, Scott A. Przybelski, Giulia Quattrini, Eric Reiman, Susan Resnick, Patricia A. Reuter-Lorenz, Jenny R. Rieck, Silvia Rios-Romenets, Karen Rodrigue, Maria Rogdaki, Melissa Rundle, Luca Sacchi, Gemma Salvadó, Gregory R. Samanez-Larkin, Michela Scamosci, Jolien Schaeverbeke, Christopher G. Schwarz, Michio Senda, Sang W. Seo, Stelvio Sestini, Mahnaz Shekari, Hilmar Sigurdson, Kaycee Sink, Zhuang Song, Oscar Sotolongo-Grau, Yi Su, Pierre Tariot, Szymon Tomczyk, Petra Tomše, Cristina Tranfaglia, Maja Trošt, Federico Turkheimer, Chi Udeh-Momoh, Angela Uecker, Rik Vandenberghe, Sylvia Villeneuve, Pieter J. Visser, Devadas Vivek, Stephanie J.B. Vos, Tyler Ward, Gagan Wig, Chengjie Xiong, Dahyun Yi, David H. Zald, Jingting Zhang, and Shenjun Zhong for providing information on the datasets included in Table S3. The National Alzheimer's Coordinating Center (NACC) database is funded by National Institute on Aging/NIH (grant U24 AG072122). NACC data are contributed by the NIA-funded Alzheimer's Disease Centers (ADCs): P50 AG005131 (PI James Brewer), P50 AG005133 (PI Oscar Lopez), P50 AG005134 (PI Bradley Hyman), P50 AG005136 (PI Thomas Grabowski), P50 AG005138 (PI Mary Sano), P50 AG005142 (PI Helena Chui), P50 AG005146 (PI Marilyn Albert), P50 AG005681 (PI John Morris), P30 AG008017 (PI Jeffrey Kaye), P30 AG008051 (PI Thomas Wisniewski), P50 AG008702 (PI Scott Small), P30 AG010124 (PI John Trojanowski), P30 AG010129 (PI Charles DeCarli), P30 AG010133 (PI Andrew Saykin), P30 AG010161 (PI David Bennett), P30 AG012300 (PI Roger Rosenberg), P30 AG013846 (PI Neil Kowall), P30 AG013854 (PI Robert Vassar), P50 AG016573 (PI Frank LaFerla), P50 AG016574 (PI Ronald Petersen), P30 AG019610 (PI Eric Reiman), P50 AG023501 (PI Bruce Miller), P50 AG025688 (PI Allan Levey), P30 AG028383 (PI Linda Van Eldik), P50 AG033514 (PI Sanjay Asthana), P30 AG035982 (PI Russell Swerdlow), P50 AG047266 (PI Todd Golde), P50 AG047270 (PI Stephen Strittmatter), P50 AG047366 (PI Victor Henderson), P30 AG049638 (PI Suzanne Craft), P30 AG053760 (PI Henry Paulson), P30 AG066546 (PI Sudha Seshadri), P20 AG068024 (PI Erik Roberson), P20 AG068053 (PI Marwan Sabbagh), P20 AG068077 (PI Gary Rosenberg), P20 AG068082 (PI Angela Jefferson), P30 AG072958 (PI Heather Whitson), P30 AG072959 (PI James Leverenz). We thank Pascal Fries for insightful discussion of Figure 1, Enrico Amico, Jitka Annen, Joe Aoe, Jae Gwan Kim, Hanli Liu, Thien Nguyen, Rajakanat Panda, Tharick Pascoal, Pedro Rosa-Neto, Ekansh Sareen, and Tadashi Watabe for providing data for Figure 3, and Nikita Beliy for coding support for Figures 1 and 3. A.S. is funded by the Belgian National Fund for Scientific Research [grant 40001328, Chargée de Recherches Fonds de la Recherche Scientifique (FRS)/Fonds National de la Recherche Scientifique (FNRS)/Université de Liège/Coma Science Group GIGA]. V.D.C. is supported by the National Institutes of Health (NIH; R01MH118695) and the National Science Foundation (21124550). S.B.E. is funded by the EU Horizon 2020 Research and Innovation Program [grant agreements 945539 (HBP SGA3) and 826421 (VBC)] and the Deutsche Forschungsgemeinschaft (SFB 1451, IRTG 2150). M.V. is funded by the Ministero dell'istruzione, dell'università e della ricerca (MIUR) under the initiative 'Departments of Excellence' (Law 232/2016), by a Wellcome Trust Digital Award (215747/Z/19/Z), and by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King's College London. J.B.P. is funded by the Swedish Research Council. S.D.J. is supported by a National Health and Medical Research Council of Australia Fellowship (APP1174164). We thank Giulia Carli and Hubertus Hautzel for providing data for Table S1. We also thank Rick Adams, Marilyn Albert, Ricardo Allegri, Silvia Alonso-Lana, Andrea Arighi, Murat Bilgel, Alexa Pichet Binette, Gérard N. Bischof, Mercè Boada, Ilaria Bonoldi, Chris Brown, Min S. Byun, Stephen F. Carter, Massimo Castellani, Jaime J. Castrellon, Jiří Cerman, Kewei Chen, Gaël Chetelat, Andrea Chincarini, Patricio Chrem, Lyduine Collij, Anka Cuderman, Tarik Dahoun, Michael D. Devous, Ramon Diaz-Arrastia, Paul Donaghy, Rachelle Doody, Massimo Dottorini, Carole Dufouil, Germán Falasco, Carles Falcon, Sara B. Festini, Christopher Fowle, Peter Fox, Crystal Franklin, Jurgen Fripp, Giovanni Frisoni, Giorgio Fumagalli, Valentin Fuster on behalf of the Progression of Early Subclinical Atherosclerosis (PESA) Study Team, Daniela Galimberti, Melanie Ganz, Valentina Garibotto, Juan D. Gispert, Karl Herholz, Rainer Hinz, Russ Hornbeck, Oliver Howes, Lauren Hudswell, Jordi Huguet, Leonardo Iaccarino, Janne Isojärvi, Takeshi Iwatsubo, Sameer Jahuar, Hyemin Jang, Peter S. Jensen, Sterling Johnson, Kristen Kennedy, David S. Knopman, Pamela LaMontagne, Susan Landau, Jessica Langbaum, Rachael Lawson, Dong Y. Lee, Francisco Lopera, Hanzhang Lu, Emma Luckett, Maura Malpetti, Marta Marquié, Robert McCutcheon, Ian M. McDonough, Richard McIntyre, Patrizia Mecocci, Lefkos Middleton, Yasuhiko Mikari, Valeria Mondelli, Silvia Morbelli, Alice Murphy, Maria A. Nettis, Flavio Nobili, Martin Nørgaard, Matthew Nour, Lauri Nummenmaa, John O'Brien, Grégory Operto, Rik Ossenkoppele, Carmine Pariante, Denise Park, Matej Perovnik, Michela Pievani, Thad Polk, Luca Presotto, Scott A. Przybelski, Giulia Quattrini, Eric Reiman, Susan Resnick, Patricia A. Reuter-Lorenz, Jenny R. Rieck, Silvia Rios-Romenets, Karen Rodrigue, Maria Rogdaki, Melissa Rundle, Luca Sacchi, Gemma Salvadó, Gregory R. Samanez-Larkin, Michela Scamosci, Jolien Schaeverbeke, Christopher G. Schwarz, Michio Senda, Sang W. Seo, Stelvio Sestini, Mahnaz Shekari, Hilmar Sigurdson, Kaycee Sink, Zhuang Song, Oscar Sotolongo-Grau, Yi Su, Pierre Tariot, Szymon Tomczyk, Petra Tomše, Cristina Tranfaglia, Maja Trošt, Federico Turkheimer, Chi Udeh-Momoh, Angela Uecker, Rik Vandenberghe, Sylvia Villeneuve, Pieter J. Visser, Devadas Vivek, Stephanie J.B. Vos, Tyler Ward, Gagan Wig, Chengjie Xiong, Dahyun Yi, David H. Zald, Jingting Zhang, and Shenjun Zhong for providing information on the datasets included in Table S3. The National Alzheimer's Coordinating Center (NACC) database is funded by National Institute on Aging/NIH (grant U24 AG072122). NACC data are contributed by the NIA-funded Alzheimer's Disease Research Centers (ADCs): P50 AG005131 (PI James Brewer), P50 AG005133 (PI Oscar Lopez), P50 AG005134 (PI Bradley Hyman), P50 AG005136 (PI Thomas Grabowski), P50 AG005138 (PI Mary Sano), P50 AG005142 (PI Helena Chui), P50 AG005146 (PI Marilyn Albert), P50 AG005681 (PI John Morris), P30 AG008017 (PI Jeffrey Kaye), P30 AG008051 (PI Thomas Wisniewski), P50 AG008702 (PI Scott Small), P30 AG010124 (PI John Trojanowski), P30 AG010129 (PI Charles DeCarli), P30 AG010133 (PI Andrew Saykin), P30 AG010161 (PI David Bennett), P30 AG012300 (PI Roger Rosenberg), P30 AG013846 (PI Neil Kowall), P30 AG013854 (PI Robert Vassar), P50 AG016573 (PI Frank LaFerla), P50 AG016574 (PI Ronald Petersen), P30 AG019610 (PI Eric Reiman), P50 AG023501 (PI Bruce Miller), P50 AG025688 (PI Allan Levey), P30 AG028383 (PI Linda Van Eldik), P50 AG033514 (PI Sanjay Asthana), P30 AG035982 (PI Russell Swerdlow), P50 AG047266 (PI Todd Golde), P50 AG047270 (PI Stephen Strittmatter), P50 AG047366 (PI Victor Henderson), P30 AG049638 (PI Suzanne Craft), P30 AG053760 (PI Henry Paulson), P30 AG066546 (PI Sudha Seshadri), P20 AG068024 (PI Erik Roberson), P20 AG068053 (PI Marwan Sabbagh), P20 AG068077 (PI Gary Rosenberg), P20 AG068082 (PI Angela Jefferson), P30 AG072958 (PI Heather Whitson), P30 AG072959 (PI James Leverenz). We thank Pascal Fries for insightful discussion of Figure 1, Enrico Amico, Jitka Annen, Joe Aoe, Jae Gwan Kim, Hanli Liu, Thien Nguyen, Rajakanat Panda, Tharick Pascoal, Pedro Rosa-Neto, Ekansh Sareen, and Tadashi Watabe for providing data for Figure 3, and Nikita Beliy for coding support for Figures 1 and 3. The authors declare no conflicts of interest.A.S. is funded by the Belgian National Fund for Scientific Research [grant 40001328 , Chargée de Recherches Fonds de la Recherche Scientifique (FRS)/Fonds National de la Recherche Scientifique (FNRS)/Université de Liège/Coma Science Group GIGA]. V.D.C. is supported by the National Institutes of Health (NIH; R01MH118695 ) and the National Science Foundation ( 21124550 ). S.B.E. is funded by the EU Horizon 2020 Research and Innovation Program [grant agreements 945539 (HBP SGA3) and 826421 (VBC)] and the Deutsche Forschungsgemeinschaft ( SFB 1451 , IRTG 2150 ). M.V. is funded by the Ministero dell'istruzione, dell'università e della ricerca ( MIUR ) under the initiative 'Departments of Excellence' (Law 232/2016), by a Wellcome Trust Digital Award ( 215747/Z/19/Z ), and by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King's College London. J.B.P. is funded by the Swedish Research Council. S.D.J. is supported by a National Health and Medical Research Council of Australia Fellowship ( APP1174164 ). We thank Giulia Carli and Hubertus Hautzel for providing data for Table S1. We also thank Rick Adams, Marilyn Albert, Ricardo Allegri, Silvia Alonso-Lana, Andrea Arighi, Murat Bilgel, Alexa Pichet Binette, Gérard N. Bischof, Mercè Boada, Ilaria Bonoldi, Chris Brown, Min S. Byun, Stephen F. Carter, Massimo Castellani, Jaime J. Castrellon, Jiří Cerman, Kewei Chen, Gaël Chetelat, Andrea Chincarini, Patricio Chrem, Lyduine Collij, Anka Cuderman, Tarik Dahoun, Michael D. Devous, Ramon Diaz-Arrastia, Paul Donaghy, Rachelle Doody, Massimo Dottorini, Carole Dufouil, Germán Falasco, Carles Falcon, Sara B. Festini, Christopher Fowle, Peter Fox, Crystal Franklin, Jurgen Fripp, Giovanni Frisoni, Giorgio Fumagalli, Valentin Fuster on behalf of the Progression of Early Subclinical Atherosclerosis (PESA) Study Team, Daniela Galimberti, Melanie Ganz, Valentina Garibotto, Juan D. Gispert, Karl Herholz, Rainer Hinz, Russ Hornbeck, Oliver Howes, Lauren Hudswell, Jordi Huguet, Leonardo Iaccarino, Janne Isojärvi, Takeshi Iwatsubo, Sameer Jahuar, Hyemin Jang, Peter S. Jensen, Sterling Johnson, Kristen Kennedy, David S. Knopman, Pamela LaMontagne, Susan Landau, Jessica Langbaum, Rachael Lawson, Dong Y. Lee, Francisco Lopera, Hanzhang Lu, Emma Luckett, Maura Malpetti, Marta Marquié, Robert McCutcheon, Ian M. McDonough, Richard McIntyre, Patrizia Mecocci, Lefkos Middleton, Yasuhiko Mikari, Valeria Mondelli, Silvia Morbelli, Alice Murphy, Maria A. Nettis, Flavio Nobili, Martin Nørgaard, Matthew Nour, Lauri Nummenmaa, John O'Brien, Grégory Operto, Rik Ossenkoppele, Carmine Pariante, Denise Park, Matej Perovnik, Michela Pievani, Thad Polk, Luca Presotto, Scott A. Przybelski, Giulia Quattrini, Eric Reiman, Susan Resnick, Patricia A. Reuter-Lorenz, Jenny R. Rieck, Silvia Rios-Romenets, Karen Rodrigue, Maria Rogdaki, Melissa Rundle, Luca Sacchi, Gemma Salvadó, Gregory R. Samanez-Larkin, Michela Scamosci, Jolien Schaeverbeke, Christopher G. Schwarz, Michio Senda, Sang W. Seo, Stelvio Sestini, Mahnaz Shekari, Hilmar Sigurdson, Kaycee Sink, Zhuang Song, Oscar Sotolongo-Grau, Yi Su, Pierre Tariot, Szymon Tomczyk, Petra Tomše, Cristina Tranfaglia, Maja Trošt, Federico Turkheimer, Chi Udeh-Momoh, Angela Uecker, Rik Vandenberghe, Sylvia Villeneuve, Pieter J. Visser, Devadas Vivek, Stephanie J.B. Vos, Tyler Ward, Gagan Wig, Chengjie Xiong, Dahyun Yi, David H. Zald, Jingting Zhang, and Shenjun Zhong for providing information on the datasets included in Table S3. The National Alzheimer's Coordinating Center (NACC) database is funded by National Institute on Aging/NIH (grant U24 AG072122 ). NACC data are contributed by the NIA-funded Alzheimer's Disease Research Centers ( ADCs ): P50 AG005131 (PI James Brewer), P50 AG005133 (PI Oscar Lopez), P50 AG005134 (PI Bradley Hyman), P50 AG005136 (PI Thomas Grabowski), P50 AG005138 (PI Mary Sano), P50 AG005142 (PI Helena Chui), P50 AG005146 (PI Marilyn Albert), P50 AG005681 (PI John Morris), P30 AG008017 (PI Jeffrey Kaye), P30 AG008051 (PI Thomas Wisniewski), P50 AG008702 (PI Scott Small), P30 AG010124 (PI John Trojanowski), P30 AG010129 (PI Charles DeCarli), P30 AG010133 (PI Andrew Saykin), P30 AG010161 (PI David Bennett), P30 AG012300 (PI Roger Rosenberg), P30 AG013846 (PI Neil Kowall), P30 AG013854 (PI Robert Vassar), P50 AG016573 (PI Frank LaFerla), P50 AG016574 (PI Ronald Petersen), P30 AG019610 (PI Eric Reiman), P50 AG023501 (PI Bruce Miller), P50 AG025688 (PI Allan Levey), P30 AG028383 (PI Linda Van Eldik), P50 AG033514 (PI Sanjay Asthana), P30 AG035982 (PI Russell Swerdlow), P50 AG047266 (PI Todd Golde), P50 AG047270 (PI Stephen Strittmatter), P50 AG047366 (PI Victor Henderson), P30 AG049638 (PI Suzanne Craft), P30 AG053760 (PI Henry Paulson), P30 AG066546 (PI Sudha Seshadri), P20 AG068024 (PI Erik Roberson), P20 AG068053 (PI Marwan Sabbagh), P20 AG068077 (PI Gary Rosenberg), P20 AG068082 (PI Angela Jefferson), P30 AG072958 (PI Heather Whitson), P30 AG072959 (PI James Leverenz). We thank Pascal Fries for insightful discussion of Figure 1 , Enrico Amico, Jitka Annen, Joe Aoe, Jae Gwan Kim, Hanli Liu, Thien Nguyen, Rajakanat Panda, Tharick Pascoal, Pedro Rosa-Neto, Ekansh Sareen, and Tadashi Watabe for providing data for Figure 3 , and Nikita Beliy for coding support for Figures 1 and 3 .A.S. is funded by the Belgian National Fund for Scientific Research [grant 40001328 , Chargée de Recherches Fonds de la Recherche Scientifique (FRS)/Fonds National de la Recherche Scientifique (FNRS)/Université de Liège/Coma Science Group GIGA]. V.D.C. is supported by the National Institutes of Health (NIH; R01MH118695 ) and the National Science Foundation ( 21124550 ). S.B.E. is funded by the EU Horizon 2020 Research and Innovation Program [grant agreements 945539 (HBP SGA3) and 826421 (VBC)] and the Deutsche Forschungsgemeinschaft ( SFB 1451 , IRTG 2150 ). M.V. is funded by the Ministero dell'istruzione, dell'università e della ricerca ( MIUR ) under the initiative 'Departments of Excellence' (Law 232/2016), by a Wellcome Trust Digital Award ( 215747/Z/19/Z ), and by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King's College London. J.B.P. is funded by the Swedish Research Council. S.D.J. is supported by a National Health and Medical Research Council of Australia Fellowship ( APP1174164 ). We thank Giulia Carli and Hubertus Hautzel for providing data for Table S1 . We also thank Rick Adams, Marilyn Albert, Ricardo Allegri, Silvia Alonso-Lana, Andrea Arighi, Murat Bilgel, Alexa Pichet Binette, Gérard N. Bischof, Mercè Boada, Ilaria Bonoldi, Chris Brown, Min S. Byun, Stephen F. Carter, Massimo Castellani, Jaime J. Castrellon, Jiří Cerman, Kewei Chen, Gaël Chetelat, Andrea Chincarini, Patricio Chrem, Lyduine Collij, Anka Cuderman, Tarik Dahoun, Michael D. Devous, Ramon Diaz-Arrastia, Paul Donaghy, Rachelle Doody, Massimo Dottorini, Carole Dufouil, Germán Falasco, Carles Falcon, Sara B. Festini, Christopher Fowle, Peter Fox, Crystal Franklin, Jurgen Fripp, Giovanni Frisoni, Giorgio Fumagalli, Valentin Fuster on behalf of the Progression of Early Subclinical Atherosclerosis (PESA) Study Team, Daniela Galimberti, Melanie Ganz, Valentina Garibotto, Juan D. Gispert, Karl Herholz, Rainer Hinz, Russ Hornbeck, Oliver Howes, Lauren Hudswell, Jordi Huguet, Leonardo Iaccarino, Janne Isojärvi, Takeshi Iwatsubo, Sameer Jahuar, Hyemin Jang, Peter S. Jensen, Sterling Johnson, Kristen Kennedy, David S. Knopman, Pamela LaMontagne, Susan Landau, Jessica Langbaum, Rachael Lawson, Dong Y. Lee, Francisco Lopera, Hanzhang Lu, Emma Luckett, Maura Malpetti, Marta Marquié, Robert McCutcheon, Ian M. McDonough, Richard McIntyre, Patrizia Mecocci, Lefkos Middleton, Yasuhiko Mikari, Valeria Mondelli, Silvia Morbelli, Alice Murphy, Maria A. Nettis, Flavio Nobili, Martin Nørgaard, Matthew Nour, Lauri Nummenmaa, John O'Brien, Grégory Operto, Rik Ossenkoppele, Carmine Pariante, Denise Park, Matej Perovnik, Michela Pievani, Thad Polk, Luca Presotto, Scott A. Przybelski, Giulia Quattrini, Eric Reiman, Susan Resnick, Patricia A. Reuter-Lorenz, Jenny R. Rieck, Silvia Rios-Romenets, Karen Rodrigue, Maria Rogdaki, Melissa Rundle, Luca Sacchi, Gemma Salvadó, Gregory R. Samanez-Larkin, Michela Scamosci, Jolien Schaeverbeke, Christopher G. Schwarz, Michio Senda, Sang W. Seo, Stelvio Sestini, Mahnaz Shekari, Hilmar Sigurdson, Kaycee Sink, Zhuang Song, Oscar Sotolongo-Grau, Yi Su, Pierre Tariot, Szymon Tomczyk, Petra Tomše, Cristina Tranfaglia, Maja Trošt, Federico Turkheimer, Chi Udeh-Momoh, Angela Uecker, Rik Vandenberghe, Sylvia Villeneuve, Pieter J. Visser, Devadas Vivek, Stephanie J.B. Vos, Tyler Ward, Gagan Wig, Chengjie Xiong, Dahyun Yi, David H. Zald, Jingting Zhang, and Shenjun Zhong for providing information on the datasets included in Table S3 . The National Alzheimer's Coordinating Center (NACC) database is funded by National Institute on Aging/NIH (grant U24 AG072122 ). NACC data are contributed by the NIA-funded Alzheimer's Disease Centers ( ADCs ): P50 AG005131 (PI James Brewer), P50 AG005133 (PI Oscar Lopez), P50 AG005134 (PI Bradley Hyman), P50 AG005136 (PI Thomas Grabowski), P50 AG005138 (PI Mary Sano), P50 AG005142 (PI Helena Chui), P50 AG005146 (PI Marilyn Albert), P50 AG005681 (PI John Morris), P30 AG008017 (PI Jeffrey Kaye), P30 AG008051 (PI Thomas Wisniewski), P50 AG008702 (PI Scott Small), P30 AG010124 (PI John Trojanowski), P30 AG010129 (PI Charles DeCarli), P30 AG010133 (PI Andrew Saykin), P30 AG010161 (PI David Bennett), P30 AG012300 (PI Roger Rosenberg), P30 AG013846 (PI Neil Kowall), P30 AG013854 (PI Robert Vassar), P50 AG016573 (PI Frank LaFerla), P50 AG016574 (PI Ronald Petersen), P30 AG019610 (PI Eric Reiman), P50 AG023501 (PI Bruce Miller), P50 AG025688 (PI Allan Levey), P30 AG028383 (PI Linda Van Eldik), P50 AG033514 (PI Sanjay Asthana), P30 AG035982 (PI Russell Swerdlow), P50 AG047266 (PI Todd Golde), P50 AG047270 (PI Stephen Strittmatter), P50 AG047366 (PI Victor Henderson), P30 AG049638 (PI Suzanne Craft), P30 AG053760 (PI Henry Paulson), P30 AG066546 (PI Sudha Seshadri), P20 AG068024 (PI Erik Roberson), P20 AG068053 (PI Marwan Sabbagh), P20 AG068077 (PI Gary Rosenberg), P20 AG068082 (PI Angela Jefferson), P30 AG072958 (PI Heather Whitson), P30 AG072959 (PI James Leverenz). We thank Pascal Fries for insightful discussion of Figure 1 , Enrico Amico, Jitka Annen, Joe Aoe, Jae Gwan Kim, Hanli Liu, Thien Nguyen, Rajakanat Panda, Tharick Pascoal, Pedro Rosa-Neto, Ekansh Sareen, and Tadashi Watabe for providing data for Figure 3 , and Nikita Beliy for coding support for Figures 1 and 3 .
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