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Higher CSF sTNFR1-related proteins associate with better prognosis in very early Alzheimer’s disease

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-021-24220-7

2041-1723

William T. Hu, Tuğba Öztürk, Alexander Kollhoff, Whitney Wharton, J. Christina Howell, 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, Zaven Kachaturian, Maria Carrillo, William Z. Potter, Lisa L. Barnes, Marie Bernard, Héctor Alfredo Baptista González, Carole Ho, John Hsiao, Eliezer Masliah, Donna Masterman, Ozioma C. Okonkwo, Laurie Ryan, Nina Silverberg, Adam Fleisher, Tom Montine, Jeffrey Kaye, Lisa Silbert, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, James Brewer, Judith L. Heidebrink, David S. Knopman, Javier Villanueva‐Meyer, Rachelle S. Doody, Joseph S. Kass, Yaakov Stern, Lawrence S. Honig, Akiva Mintz, Beau M. Ances, Mark A. Mintun, David Geldmacher, Marissa Natelson Love, Hillel Grossman, Martin Goldstein, Raj C. Shah, Melissa Lamar, Ranjan Duara, Maria T. Greig‐Custo, Marilyn Albert, Chiadi U. Onyike, Amanda Smith, Martin Sadowski, Thomas Wısnıewskı, Melanie Shulman, P. Murali Doraiswamy, Jeffrey R. Petrella, Olga James, Jason Karlawish, David A. Wolk, Charles D. Smith, Gregory A. Jicha, Riham El Khouli, Oscar L. López, Anton P. Porsteinsson, Gaby Thai, Aimee Pierce, Brendan Kelley, Trung Nguyen, Kyle Womack, Allan I. Levey, James J. Lah, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Daniel Silverman, Sarah Kremen, Neill R. Graff‐Radford, Martin R. Farlow, Christopher H. van Dyck, Adam P. Mecca, Howard Chertkow, Susan Vaitekunis, Sandra E. Black, Bojana Stefanovic, Chris Heyn, Ging‐Yuek Robin Hsiung, Vesna Sossi, Elizabeth Finger, Stephen Pasternak, Irina Rachinsky, Ian Grant, Emily Rogalskı, M.‐Marsel Mesulam, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Howard J. Rosen, Bruce L. Miller, David C. Perry, Raymond Scott Turner, Reisa A. Sperling, Keith A. Johnson, Gad A. Marshall, Jerome A. Yesavage, Joy L. Taylor, Steven Chao, Christine M. Belden, Alireza Atri, Bryan M. Spann, Ronald Killiany, Robert A. Stern, Jesse Mez, Thomas O. Obisesan, Oyonumo Ntekim, Alan J. Lerner, Paula Ogrocki, Curtis Tatsuoka, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Vernice Bates, Horacio Capote, Michael Borrie, T.-Y. Lee, Robert Bartha, Sterling C. Johnson, Sanjay Asthana, Cynthia M. Carlsson, Allison Perrin, Douglas W. Scharre, Maria Kataki, Rawan Tarawneh, David Hart, Earl A. Zimmerman, Dzintra Celmins, Del D. Miller, Hristina Koleva, Hyungsub Shim, Jeff D. Williamson, Suzanne Craft, Jo Cleveland, Brian R. Ott, Jonathan Drake, Geoffrey Tremont, Marwan N. Sabbagh, Aaron Ritter, Jacobo Mintzer, Joseph C. Masdeu, Jiong Shi, Paul Newhouse, Steven Potkin, Stephen Salloway, Paul Malloy, Stephen Correia, Smita Kittur, Godfrey D. Pearlson, Karen Blank, Laura A. Flashman, Marc Seltzer, Athena Lee, Norman Relkin, Gloria Chiang,

Dementia and Cognitive Impairment Research

Abstract Neuroinflammation is associated with Alzheimer’s disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-related groups within and across diagnostic categories in 382 participants from the Alzheimer’s Disease Neuro-imaging Initiative as well participants from two independent cohorts. We further show higher levels of proteins related to soluble tumor necrosis factor receptor 1 are associated with reduced risk of conversion to dementia in the multi-centered ( p = 0.027) and independent ( p = 0.038) cohorts of people with mild cognitive impairment due to predicted Alzheimer’s disease, while higher soluble TREM2 levels associated with slower decline in the dementia stage of Alzheimer’s disease. These inflammatory proteins thus provide prognostic information independent of established Alzheimer’s markers.