Plasma phosphorylated-tau181 as a predictive biomarker for Alzheimer’s amyloid, tau and FDG PET status

著者: Xue‐Ning Shen, Yuyuan Huang, Shi-Dong Chen, Yu Guo, Lan Tan, Qiang Dong, Jin‐Tai Yu, Alzheimer’s Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William J. Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John C. Morris, Richard J. Perrin, Leslie M. Shaw, María C. Carrillo, William C. Potter, Lisa L. Barnes, Marie Bernard, Hector M. González, Carole Ho, John K. Hsiao, Jonathan Jackson, Eliezer Masliah, Donna Masterman, Ozioma C. Okonkwo, Richard Perrin, Laurie Ryan, Nina Silverberg, Adam Fleisher, Juliet Fockler, Cat Conti, Dallas P. Veitch, John Neuhaus, Chengshi Jin, Rachel L. Nosheny, Miriam T. Ashford, Derek Flenniken, Adrienne Kormos, Gustavo Jiménez, Michael Donohue, Devon Gessert, Jennifer Salazar, Caileigh Zimmerman, Yuliana Cabrera, Sarah Walter, Garrett Miller, Godfrey Coker, Taylor Clanton, Lindsey Hergesheimer, Stephanie Smith, Olusegun Adegoke, Payam Mahboubi, Shelley Moore, Jeremy Pizzola, Elizabeth Shaffer, Brittany Sloan, Danielle Harvey, Bret Borowski, Chad Ward, Christopher G. Schwarz, David Jones, Jeff Gunter, Kejal Kantarci, Matthew L. Senjem, Prashanthi Vemuri, Robert C. Reid, Nick C. Fox, Ian B. Malone, Paul M. Thompson, Sophia I. Thomopoulos, Talia M. Nir, Neda Jahanshad, Charles DeCarli, Alexander Knaack, Evan Fletcher, Duygu Tosun, Stephanie Rossi Chen, Mark Choe, Karen Crawford, Paul A. Yushkevich, Sandhitsu R. Das, Robert A. Koeppe, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, Richard Perrin, Nigel J. Cairns, Erin Householder, Erin Franklin, Haley Bernhardt, Lisa Taylor‐Reinwald, Leslie M. Shaw, John Q. Trojanowki, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Andrew J. Saykin, Kwangsik Nho, Shannon L. Risacher, Liana G. Apostolova, Li Shen, Tatiana Foroud, Kelly Nudelman, Kelley Faber, Kristi Wilmes, Leon J. Thal, Zaven S. Khachaturian, John K. Hsiao, Lisa C. Silbert, Betty Lind, Rachel Crissey, Jeffrey Kaye, Raina Carter, Sara Dolen, Joseph Quinn, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Karen Dagerman, Bryan M. Spann, James B. Brewer, Helen Vanderswag, Adam Fleisher, Jaimie Ziolkowski, Judith L. Heidebrink, Lisa Zbizek-Nulph, Joanne Lord, Colleen S. Albers, David S. Knopman, Kris Johnson, Javier Villanueva‐Meyer, Valory Pavlik, Nathaniel Pacini, Ashley Lamb, Joseph S. Kass, Rachelle S. Doody, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Akiva Mintz, Beau M. Ances, David Winkfield, Maria Carroll, Georgia Stobbs-Cucchi, Angela Oliver, Mary L. Creech, Mark A. Mintun, Stacy Schneider, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Daniel Marson, Hillel Grossman, Martin Goldstein, Jonathan Greenberg, Effie Mitsis, Raj C. Shah, Melissa Lamar, Patricia Samuels, Ranjan Duara, Maria T. Greig‐Custo, Rosemarie Rodriguez, Marilyn Albert, Chiadi Onyike, Leonie Farrington, Scott Rudow, Rottislav Brichko, Stephanie Kielb, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Martin Sadowski, Thomas Wısnıewskı, Melanie Shulman, Arline Faustin, Julia Rao, Karen M. Castro, Anaztasia Ulysse, Shannon Chen, Mohammed O. Sheikh, Jamika Singleton-Garvin, P. Murali Doraiswamy, Jeffrey R. Petrella, Olga James, Terence Z. Wong, Salvador Borges‐Neto, Jason H. Karlawish, David A. Wolk, Sanjeev Vaishnavi, Christopher M. Clark, Steven E. Arnold, Charles D. Smith, Gregory A. Jicha, Riham El Khouli, Flavius D. Raslau, Oscar L. López, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Kim Martin, Nancy Kowalski, Melanie Keltz, Bonnie S. Goldstein, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Gaby Thai, Aimee Pierce, Beatriz Yanez, Elizabeth Sosa, Megan Witbracht, Brendan Kelley, Trung Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Ihab Hajjar, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Daniel Silverman, Sarah Kremen, Liana G. Apostolova, Kathleen Tingus, Po H. Lu, George Bartzokis, Ellen Woo, Edmond Teng, Neill R. Graff‐Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Adam P. Mecca, Susan P. Good, Martha G. MacAvoy, Richard E. Carson, Pradeep Varma, Howard Chertkow, Susan Vaitekunis, Chris Hosein, Sandra Black, Bojana Stefanovic, Chris Heyn, Ging‐Yuek Robin Hsiung, Ellen Kim, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternak, Irina Rachinsky, Andrew Kertesz, Dick Drost, John Rogers, Ian Grant, Brittanie Muse, Emily Rogalskı, Jordan Robson, M.‐Marsel Mesulam, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Kristine Lipowski, Sandra Weıntraub, Borna Bonakdarpour, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Howard J. Rosen, Bruce L. Miller, David C. Perry, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Kelly McCann, Jessica Poe, Reisa A. Sperling, Keith A. Johnson, Gad A. Marshall, Christine M. Belden, Alireza Atri, Bryan M. Spann, Kelly A. Clark, Edward Zamrini, Marwan N. Sabbagh, Ronald Killiany, Robert A. Stern, Jesse Mez, Neil W. Kowall, Andrew E. Budson, Thomas O. Obisesan, Oyonumo Ntekim, Saba Wolday, Javed Khan, Evaristus Nwulia, Sheeba Nadarajah, Alan J. Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Vernice Bates, Horacio Capote, Michelle Rainka, Michael Borrie, T‐Y Lee, Robert Bartha, Sterling C. Johnson, Sanjay Asthana, Cynthia M. Carlsson, Allison Perrin, Anna Burke, Douglas W. Scharre, Maria Kataki, Rawan Tarawneh, Brendan Kelley, David Hart, Earl A. Zimmerman, Dzintra Celmins, Del D. Miller, Laura L. Boles Ponto, Karen Ekstam Smith, Hristina Koleva, Hyungsub Shim, Ki Won Nam, Susan K. Schultz, Jeff D. Williamson, Suzanne Craft, Jo Cleveland, Mia Yang, Kaycee M. Sink, Brian R. Ott, Jonathan Drake, Geoffrey Tremont, Lori A. Daiello, Jonathan Drake, Marwan N. Sabbagh, Aaron Ritter, Charles Bernick, Donna Munic, Akiva Mintz, Abigail O’Connelll, Jacobo Mintzer, Arthur Wiliams, Joseph C. Masdeu, Jiong Shi, Angelica Garcia, Marwan N. Sabbagh, Paul Newhouse, Steven G. Potkin, Stephen Salloway, Paul Malloy, Stephen Correia, Smita Kittur, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Athena Lee, Ron Petersen, Thomas C. Neylan, Jordan Grafman, Tom Montine, Sarah Danowski, Catherine Nguyen-Barrera, Shannon Finley, Danielle Harvey, Michael Donohue, Matt A. Bernstein, Norm Foster, Tatiana Foroud, Steven G. Potkin, Li Shen, Kelley Faber, Sung Eun Kim, Kwangsik Nho, Kristi Wilmes, Helen Vanderswag, Adam Fleisher, Ajay Sood, Kimberly S. Blanchard, Debra Fleischman, Maria T. Greig, Bonnie S. Goldstein, Kimberly S. Martin, Gaby Thai, Aimee Pierce, Christopher Reist, Beatriz Yanez, Elizabeth Sosa, Megan Witbracht, Carl Sadowsky, Walter Martínez, Teresa Villena, Howard J. Rosen, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Joy L. Taylor, Steven Chao, Jaila Coleman, Jessica D. White, Barton Lane, Allyson Rosen, Jared Tinklenberg, Gustavo Jimenez‐Maggiora, Erin Drake, Mike Donohue, Craig Nelson, David Bickford, Meryl A. Butters, Michelle Zmuda, Bret Borowski, Jeff Gunter, Matthew L. Senjem, Kejal Kantarci, Chad Ward, Denise A. Reyes, Kelley Faber, Kelly Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, Dariella Fernandez, Michelle Zmuda - Translational Psychiatry 2021 被引用: 70

Plasma phosphorylated-tau181 (p-tau181) showed the potential for Alzheimer's diagnosis and prognosis, but its role in detecting cerebral pathologies is unclear. We aimed to evaluate whether it could serve as a marker for Alzheimer's pathology in the brain. A total of 1189 participants with plasma p-tau181 and PET data of amyloid, tau or FDG PET were included from ADNI. Cross-sectional relationships of plasma p-tau181 with PET biomarkers were tested. Longitudinally, we further investigated whether different p-tau181 levels at baseline predicted different progression of Alzheimer's pathological changes in the brain. We found plasma p-tau181 significantly correlated with brain amyloid (Spearman ρ = 0.45, P < 0.0001), tau (0.25, P = 0.0003), and FDG PET uptakes (-0.37, P < 0.0001), and increased along the Alzheimer's continuum. Individually, plasma p-tau181 could detect abnormal amyloid, tau pathologies and hypometabolism in the brain, similar with or even better than clinical indicators. The diagnostic accuracy of plasma p-tau181 elevated significantly when combined with clinical information (AUC = 0.814 for amyloid PET, 0.773 for tau PET, and 0.708 for FDG PET). Relationships of plasma p-tau181 with brain pathologies were partly or entirely mediated by the corresponding CSF biomarkers. Besides, individuals with abnormal plasma p-tau181 level (>18.85 pg/ml) at baseline had a higher risk of pathological progression in brain amyloid (HR: 2.32, 95%CI 1.32-4.08) and FDG PET (3.21, 95%CI 2.06-5.01) status. Plasma p-tau181 may be a sensitive screening test for detecting brain pathologies, and serve as a predictive biomarker for Alzheimer's pathophysiology.