Prevalence and Clinical Implications of a β-Amyloid–Negative, Tau-Positive Cerebrospinal Fluid Biomarker Profile in Alzheimer Disease

• DOI: 10.1001/jamaneurol.2023.2338
• Publication Date: 2023-07-31T15:34:34Z
• Authors: Pontus Erickson; Joel Simrén; Wagner S. Brum; Gilda E. Ennis; Gwendlyn Kollmorgen; Ivonne Suridjan; Rebecca Langhough; Erin M. Jonaitis; Carol A. Van Hulle; Tobey J. Betthauser; Cynthia M. Carlsson; Sanjay Asthana; Nicholas J. Ashton; Sterling C. Johnson; Leslie M. Shaw; Kaj Blennow; Ulf Andreasson; Barbara B. Bendlin; Henrik Zetterberg; ; Michael Weiner; Paul Aisen; Ronald Petersen; Clifford R. Jack; William Jagust; John Q Trojanowki; Arthur W. Toga; Laurel Beckett; Robert C. Green; Andrew J. Saykin; John Morris; Leslie M. Shaw; Enchi Liu; Tom Montine; Ronald G. Thomas; Michael Donohue; Sarah Walter; Devon Gessert; Tamie Sather; Gus Jiminez; Danielle Harvey; Matthew Bernstein; Nick Fox; Paul Thompson; Norbert Schuff; Charles DeCArli; Bret Borowski; Jeff Gunter; Matt Senjem; Prashanthi Vemuri; David Jones; Kejal Kantarci; Chad Ward; Robert A. Koeppe; Norm Foster; Eric M. Reiman; Kewei Chen; Chet Mathis; Susan Landau; Nigel J. Cairns; Erin Householder; Lisa Taylor Reinwald; Virginia Lee; Magdalena Korecka; Michal Figurski; Karen Crawford; Scott Neu; Tatiana M. Foroud; Steven Potkin; Li Shen; Faber Kelley; Sungeun Kim; Kwangsik Nho; Zaven Kachaturian; Richard Frank; Peter J. J Snyder; Susan Molchan; Jeffrey Kaye; Joseph Quinn; Betty Lind; Raina Carter; Sara Dolen; Lon S. Schneider; Sonia Pawluczyk; Mauricio Beccera; Liberty Teodoro; Bryan M. M Spann; James Brewer; Helen Vanderswag; Adam Fleisher; Judith L Heidebrink; Joanne L Lord; Sara Mason; Colleen Albers; David Knopman; Kris Johnson; Rachelle S Doody; Javier Villanueva...; Munir Chowdhury; Susan Rountree; Mimi Dang; Yaakov Stern; Lawrence S Honig; Karen L Bell; Beau Ances; John C Morris; Maria Carroll; Sue Leon; Mark A Mintun; Stacy Schneider; Angela OliverNG; Randall Griffith; David Clark; David Geldmacher; John Brockington; Erik Roberson; Hillel Grossman; Effie Mitsis; Leyla deToledo-Mo...; Raj C Shah; Ranjan Duara; Daniel Varon; Maria T Greig; Peggy Roberts; Marilyn Albert; Chiadi Onyike; Daniel D’Agostino; Stephanie Kielb; James E Galvin; Dana M Pogorelec; Brittany Cerbone; Christina A Michel; Henry Rusinek; Mony J de Leon; Lidia Glodzik; Susan De Santi; P Murali Doraiswamy; Jeffrey R Petrella; Terence Z Wong; Steven E Arnold; Jason H Karlawish; David Wolk; Charles D Smith; Greg Jicha; Peter Hardy; Partha Sinha; Elizabeth Oates; Gary Conrad; Oscar Lopez; MaryAnn Oakley; Donna Simpson; Anton Porsteinsson; Bonnie Goldstein; Kim Martin; Kelly Makino; M Saleem Ismail; Connie Brand; Ruth Mulnard; Gaby Thai; Catherine Mc Adam...; Kyle Womack; Dana Mathews; Mary Quiceno; Ramon Diaz Arrastia; Richard King; Myron Weiner; Kristen Martin Cook; Michael DeVous; Allan Levey; James Lah; Janet Cellar; Jeffrey Burns; Heather Anderson; Russell Swerdlow; Liana Apostolova; Kathleen Tingus; Ellen Woo; Daniel Silverman; Po Lu; George Bartzokis; Neill Graff Radford; Francine ParfittH; Tracy Kendall; Heather Johnson; Martin Farlow; Ann Marie Hake; Brandy Matthews; Scott Herring; Cynthia Hunt; Christopher van Dyck; Richard Carson; Martha G MacAvoy; Howard Chertkow; Howard Bergman; Chris Hosein; Sandra Black; Bojana Stefanovic; Curtis Caldwell; Ging Yuek Robin H...; Howard Feldman; Benita Mudge; Michele Assaly Past; Andrew Kertesz; John Rogers; Dick Trost; Charles Bernick; Donna Munic; Diana Kerwin; Marek Marsel Mesulam; Kristine Lipowski; Chuang Kuo Wu; Nancy Johnson; Carl Sadowsky; Walter Martinez; Teresa Villena; Raymond Scott Turner; Kathleen Johnson; Brigid Reynolds; Reisa A Sperling; Keith A Johnson; Gad Marshall; Meghan Frey; Jerome Yesavage; Joy L Taylor; Barton Lane; Allyson Rosen; Jared Tinklenberg; Marwan N Sabbagh; Christine M Belden; Sandra A Jacobson; Sherye A Sirrel; Neil Kowall; Ronald Killiany; Andrew E Budson; Alexander Norbash; Patricia Lynn Joh...; Thomas O Obisesan; Saba Wolday; Joanne Allard; Alan Lerner; Paula Ogrocki; Leon Hudson; Evan Fletcher; Owen Carmichael; John Olichney; Charles DeCarli; Smita Kittur; Michael Borrie; T Y Lee; Rob Bartha; Sterling Johnson; Sanjay Asthana; Cynthia M Carlsson; Steven G G Potkin; Adrian Preda; Dana Nguyen; Pierre Tariot; Stephanie Reeder; Vernice Bates; Horacio Capote; Michelle Rainka; Douglas W Scharre; Maria Kataki; Anahita Adeli; Earl A Zimmerman; Dzintra Celmins; Alice D Brown; Godfrey D Pearlson; Karen Blank; Karen Anderson; Robert B Santulli; Tamar J Kitzmiller; Eben S Schwartz; Kaycee M SinkS; Jeff D Williamson; Pradeep Garg; Franklin Watkins; Brian R Ott; Henry Querfurth; Geoffrey Tremont; Stephen Salloway; Paul Malloy; Stephen Correia; Howard J Rosen; Bruce L Miller; Jacobo Mintzer; Kenneth Spicer; David Bachman; Elizabether Finger; Stephen Pasternak; Irina Rachinsky; Dick Drost; Nunzio Pomara; Raymundo Hernando; Antero Sarrael; Susan K Schultz; Laura L Boles Ponto; Hyungsub Shim; Karen Elizabeth S...; Norman Relkin; Gloria Chaing; Lisa Raudin; Amanda Smith; Kristin Fargher; Balebail Ashok Raj
• Keywords: 0301 basic medicine; 03 medical and health sciences; Original Investigation

Importance Knowledge is lacking on the prevalence and prognosis of individuals with a β-amyloid–negative, tau-positive (A−T+) cerebrospinal fluid (CSF) biomarker profile. Objective To estimate CSF A−T+ profile investigate its clinical implications. Design, Setting, Participants This was retrospective cohort study cross-sectional multicenter University Gothenburg (UGOT) (November 2019-January 2021), longitudinal Alzheimer Disease Neuroimaging Initiative (ADNI) (individuals mild cognitive impairment [MCI] no impairment; September 2005-May 2022), 2 Wisconsin cohorts, Research Center Registry for Prevention (WISC; without February 2007-November 2020). study, data collected from referral centers in routine research settings (ADNI WISC). Eligible had 1 lumbar puncture (all cohorts), or more assessments WISC), imaging only) performed separate occasions. Data were analyzed August 2022 to April 2023. Exposures Baseline Aβ42/40 phosphorylated tau (p-tau)181; tests (ADNI: modified preclinical composite [mPACC]; WISC: 3-test PACC [PACC-3]). ADNI included [ 18 F]-florbetapir amyloid positron emission tomography (PET), magnetic resonance (MRI), F]-fluorodeoxyglucose PET (FDG-PET), tau-PET F]-flortaucipir, F]-MK6240). Main Outcomes Measures Primary outcomes AT profiles continuous global outcome trajectories vs A−T− groups. Secondary tau-PET. Results A total 7679 (mean [SD] age, 71.0 [8.4] years; 4101 male [53%]) UGOT cohort, 970 73 [7.0] 526 [54%]) 519 60 [7.3] 346 female [67%]) WISC cohort. The an 4.1% (95% CI, 3.7%-4.6%), being less common than other patterns. Longitudinally, significant differences rates worsening observed between cognition biomarkers. Cross-sectionally, similar uptake Conclusion Relevance suggest that found approximately 5% punctures not associated higher rate decline signs disease progression compared biomarker-negative individuals.