Higher CSF sTNFR1-related proteins associate with better prognosis in very early Alzheimer’s disease
William T. Hu(Rutgers, The State University of New Jersey), Tuğba Öztürk(Emory University), Alexander Kollhoff(Emory University), Whitney Wharton(Emory University), J. Christina Howell(Emory University), Alzheimer’s Disease Neuroimaging Initiative(University of California, San Francisco), Michael W. Weiner(LAC+USC Medical Center), Paul Aisen(LAC+USC Medical Center), Ronald Petersen(Mayo Clinic in Arizona), Clifford R. Jack(Berkeley College), William J. Jagust(Berkeley College), John Q. Trojanowki(LAC+USC Medical Center), Arthur W. Toga(LAC+USC Medical Center), Laurel Beckett(Brigham and Women's Hospital), Robert C. Green(Brigham and Women's Hospital), Andrew J. Saykin(Washington University in St. Louis), John C. Morris(Washington University in St. Louis), Richard J. Perrin(Washington University in St. Louis), Leslie M. Shaw(Prevent Alzheimer’s Disease 2020), Zaven Kachaturian(Alzheimer's Association), Maria Carrillo(Alzheimer's Association), William Z. Potter(National Institute of Mental Health), Lisa L. Barnes(National Institute on Aging), Marie Bernard(University of California San Diego), Héctor Alfredo Baptista González(University of California San Diego), Carole Ho(Denali Therapeutics (United States)), John Hsiao(National Institute on Aging), Eliezer Masliah(Biogen (United States)), Donna Masterman(Biogen (United States)), Ozioma C. Okonkwo(University of Wisconsin–Madison), Laurie Ryan(National Institute on Aging), Nina Silverberg(Eli Lilly (United States)), Adam Fleisher(Eli Lilly (United States)), Tom Montine(Oregon Health & Science University), Jeffrey Kaye(Oregon Health & Science University), Lisa C. Silbert(LAC+USC Medical Center), Lon S. Schneider(LAC+USC Medical Center), Sonia Pawluczyk(LAC+USC Medical Center), Mauricio Becerra(LAC+USC Medical Center), James B. Brewer(University of Michigan), Judith L. Heidebrink(University of Michigan), David S. Knopman(Baylor College of Medicine), Javier Villanueva‐Meyer(Baylor College of Medicine), Rachelle S. Doody(Baylor College of Medicine), Joseph S. Kass(Baylor College of Medicine), Yaakov Stern(Columbia University Irving Medical Center), Lawrence S. Honig(Columbia University Irving Medical Center), Akiva Mintz(Washington University in St. Louis), Beau M. Ances(Washington University in St. Louis), Mark A. Mintun(Washington University in St. Louis), David Geldmacher(University of Alabama at Birmingham), Marissa Natelson Love(University of Alabama at Birmingham), Hillel Grossman(Icahn School of Medicine at Mount Sinai), Martin Goldstein(Rush University), Raj C. Shah(Rush University), Melissa Lamar(Rush University), Ranjan Duara, Maria T. Greig‐Custo(Johns Hopkins University), Marilyn Albert(Johns Hopkins University), Chiadi U. Onyike(Johns Hopkins University), Amanda Smith(University of South Florida), Martin Sadowski(New York University), Thomas Wısnıewskı(New York University), Melanie Shulman(Duke University), P. Murali Doraiswamy(Duke University), Jeffrey R. Petrella(Duke University), Olga James(Duke University), Jason Karlawish(University of Pennsylvania), David A. Wolk(University of Kentucky), Charles D. Smith(University of Kentucky), Gregory A. Jicha(University of Kentucky), Riham El Khouli(University of Kentucky), Oscar L. López(Pittsburg State University), Anton P. Porsteinsson(UC Irvine Health), Gaby Thai(UC Irvine Health), Aimee Pierce(UC Irvine Health), Brendan Kelley(The University of Texas Southwestern Medical Center), Trung Nguyen(The University of Texas Southwestern Medical Center), Kyle Womack(The University of Texas Southwestern Medical Center), Allan I. Levey(Emory University), James J. Lah(Emory University), Jeffrey M. Burns(University of Kansas Medical Center), Russell H. Swerdlow(University of Kansas Medical Center), William M. Brooks(University of Kansas Medical Center), Daniel Silverman(UtopiaCompression (United States)), Sarah Kremen(WinnMed), Neill R. Graff‐Radford(WinnMed), Martin R. Farlow(Yale University), Christopher H. van Dyck(Yale University), Adam P. Mecca(Yale University), Howard Chertkow(McGill University), Susan Vaitekunis(Sunnybrook Health Science Centre), Sandra E. Black(Sunnybrook Health Science Centre), Bojana Stefanovic(Sunnybrook Health Science Centre), Chris Heyn(Sunnybrook Health Science Centre), Ging‐Yuek Robin Hsiung(University of British Columbia), Vesna Sossi(University of British Columbia), Elizabeth Finger(St Joseph's Health Care), Stephen Pasternak(St Joseph's Health Care), Irina Rachinsky(Northwestern University), Ian Grant(Northwestern University), Emily Rogalskı(Northwestern University), M.‐Marsel Mesulam(Northwestern University), Nunzio Pomara(Nathan Kline Institute for Psychiatric Research), Raymundo Hernando(Nathan Kline Institute for Psychiatric Research), Antero Sarrael(Nathan Kline Institute for Psychiatric Research), Howard J. Rosen(University of California, San Francisco), Bruce L. Miller(University of California, San Francisco), David C. Perry(University of California, San Francisco), Raymond Scott Turner(Brigham and Women's Hospital), Reisa A. Sperling(Brigham and Women's Hospital), Keith A. Johnson(Brigham and Women's Hospital), Gad A. Marshall(Brigham and Women's Hospital), Jerome A. Yesavage(Palo Alto University), Joy L. Taylor(Palo Alto University), Steven Chao(Palo Alto University), Christine M. Belden(Banner Health), Alireza Atri(Banner Health), Bryan M. Spann(Banner Health), Ronald Killiany, Robert A. Stern, Jesse Mez(Howard University), Thomas O. Obisesan(Howard University), Oyonumo Ntekim(Howard University), Alan J. Lerner(Case Western Reserve University), Paula Ogrocki(Case Western Reserve University), Curtis Tatsuoka(Case Western Reserve University), Evan Fletcher(University of California, Davis), Pauline Maillard(University of California, Davis), John Olichney(University of California, Davis), Charles DeCarli(Dent Neurologic Institute), Vernice Bates(Dent Neurologic Institute), Horacio Capote(Dent Neurologic Institute), Michael Borrie(Parkwood Institute), T.-Y. Lee(Parkwood Institute), Robert Bartha(University of Wisconsin–Madison), Sterling C. Johnson(University of Wisconsin–Madison), Sanjay Asthana(University of Wisconsin–Madison), Cynthia M. Carlsson(University of Wisconsin–Madison), Allison Perrin(Banner Alzheimer’s Institute), Douglas W. Scharre(The Ohio State University), Maria Kataki(The Ohio State University), Rawan Tarawneh(The Ohio State University), David Hart(Albany Medical Center Hospital), Earl A. Zimmerman(Albany Medical Center Hospital), Dzintra Celmins(University of Iowa), Del D. Miller(University of Iowa), Hristina Koleva(University of Iowa), Hyungsub Shim(University of Iowa), Jeff D. Williamson(Wake Forest University), Suzanne Craft(Wake Forest University), Jo Cleveland(Providence College), Brian R. Ott(Providence College), Jonathan Drake(Providence College), Geoffrey Tremont(Cleveland Clinic), Marwan N. Sabbagh(Cleveland Clinic), Aaron Ritter(Cleveland Clinic), Jacobo Mintzer(Houston Methodist), Joseph C. Masdeu(Houston Methodist), Jiong Shi(Barrow Neurological Institute), Paul Newhouse(California State University, Long Beach), Steven Potkin(Providence College), Stephen Salloway(Providence College), Paul Malloy(Providence College), Stephen Correia(Providence College), Smita Kittur(Hartford Hospital), Godfrey D. Pearlson(Hartford Hospital), Karen Blank(Dartmouth–Hitchcock Medical Center), Laura A. Flashman(Dartmouth–Hitchcock Medical Center), Marc Seltzer(Dartmouth–Hitchcock Medical Center), Athena Lee(Cornell University), Norman Relkin(Cornell University), Gloria Chiang(Cornell University)
Cited by 36Open Access
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.
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