Plasma Phosphorylated Tau 217 to Identify Preclinical Alzheimer Disease

作者：Gemma Salvadó, Shorena Janelidze, Divya Bali, Anna Orduña Dolado, Joseph Therriault, Wagner S. Brum, Alexa Pichet Binette, Erik Stomrud, Niklas Mattsson, Sebastian Palmqvist, Emma M. Coomans, Charlotte E. Teunissen, Wiesje M. van der Flier, Nesrine Rahmouni, Tammie L.S. Benzinger, Juan Domingo Gispert, Kaj Blennow, Vincent Doré, Azadeh Feizpour, Christopher C. Rowe, Daniel Alcolea, Juan Fortea, Sylvia Villeneuve, Sterling C. Johnson, Pedro Rosa‐Neto, Ronald C. Petersen, Clifford R. Jack, Suzanne E. Schindler, Marc Suárez‐Calvet, Rik Ossenkoppele, Oskar Hansson, ADNI, ALFA, and PREVENT-AD Study Groups, Olusegun Adegoke, Kedir Adem Hussen, Paul Aisen, Adeyinka Ajayi, Hannatu Amaza, Liana G. Apostolova, Miriam T. Ashford, Omobolanle Ayo, Lisa L. Barnes, Laurel Beckett, Marie Bernard, Haley Bernhardt, Virginia Boatwright, Bret Borowski, Magdalena Brylska, Neil Buckholtz, Yuliana Cabrera, Nigel J. Cairns, Maria Carrillo, Mark Choe, Taylor Clanton, Cat Conti, Hannah Craft, Karen Crawford, Sandhitsu R. Das, Charles DeCarli, Joseph Di Benedetto, Adam Diaz, Michael Donohue, Erin Drake, Claire M. Erickson, Kelley Faber, Joel P. Felmlee, Andrea Fidell, Derek Flenniken, Evan Fletcher, Juliet Fockler, Arvin Forghanian-Arani, Tatiana Foroud, Nick C. Fox, R.T. Frank, Erin Franklin, Matt Glittenberg, Héctor Alfredo Baptista González, Robert C. Green, Joshua D. Grill, Jeff Gunter, Vanessa Guzmán, Kristin Harkins, Danielle Harvey, Caitie Hedberg, Lindsey Hergesheimer, Carole Ho, Isabella Hoang, John Hsiao, Clifford R. Jack, Jonathan Jackson, William Jagust, Neda Jahanshad, Cecily Jenkins, Gustavo Jiménez, Chengshi Jin, Taeho Jo, Zaven Kachaturian, Rima Kaddurah-Daouk, Kejal Kantarci, Jason Karlawish, Zaven S. Khachaturian, Alexander Knaack, Robert A. Koeppe, Magdalena Korecka, Adrienne Kormos, Kaori Kubo Germano, Winnie Kwang, Kaci Lacy, Susan Landau, Emily A. Largent, Edward B. Lee, Virginia M.‐Y. Lee, Brian J. Lopresti, Fabiola Magana, Payam Mahboubi, Ian G. Malone, Eliezer Masliah, Donna Masterman, Leonard Matoush, Melanie J. Miller, Susan Molchan, Tom Montine, John Moore-Weiss, John C. Morris, Scott Neu, Kwangsik Nho, Talia M. Nir, Rachel L. Nosheny, Kelly Nudelman, Sheila Ogwang, Ozioma Okonkwo, Shaniya Parkins, Richard J. Perrin, Ronald Petersen, Jeremy Pizzola, Zoë Potter, William Z. Potter, Gil D. Rabinovici, Michael Rafii, Rema Raman, Robert W. Reid, Calvin Reyes, Denise Reyes, Shannon L. Risacher, Mónica Rivera Mindt, Justin Robison, Stephanie Rossi Chen, Laurie Ryan, Pallavi Sachdev, Naomi Saito, Jennifer Salazar, Andrew J. Saykin, Christopher G. Schwarz, Mai Seng Thao, Matthew L. Senjem, Elizabeth Shaffer, Leslie M. Shaw, Shen Li, Nina Silverberg, Stephanie Smith, Peter J. Snyder, Joe Strong, Sandra Talavera, Lisa Taylor‐Reinwald, Leon J. Thal, Lisa Thomas, Sophia I. Thomopoulos, Paul Thompson, Arthur W. Toga, Duygu Tosun, John Q. Trojanowki, Diana Truran Sacrey, Prashanthi Vemuri, Victor L. Villemagne, Sarah Walter, Yang Wan, Chad Ward, Caitlin Webb, Michael W. Weiner, Trinity Weisensel, Paul A. Yushkevich, Caileigh Zimmerman, Sylvia Villeneuve, Judes Poirier, John C.S. Breitner, Mohamed Badawy, Sylvain Baillet, Andrée‐Ann Baril, Carolina Minguillón, Ricardo A Aguilar, Annabella B Gorriti, Anna Brugulat‐Serrat, Raffaele Cacciaglia, Lidia C Gispert, Alba C Martinez, Marta del Campo, Ruth D Iglesias, Sherezade F Julian, P Serra, Armand González‐Escalante, Laura H Penas, Gema H Rodriguez, Jordi H Ninou, Laura Iglesias Gamaz, Iva Knezevic, Paula M Alvarez, Tania M Diaz, Eva Palacios, María Belén Pascual, A Ballester, Sandra P Mendez, Blanca Rodríguez‐Fernández, Laura Ros Freixedes, Aleix S Vila, Lluis S Harster, Anna S Prat, Marc V Jaramillo, Natàlia Vilor‐Tejedor · 发表于：JAMA Neurology · 年份：2025 · DOI：10.1001/jamaneurol.2025.3217 · 被引用次数：56 · 研究领域：Dementia and Cognitive Impairment Research、Alzheimer's disease research and treatments、Cancer-related cognitive impairment studies

Importance: Advances in Alzheimer disease (AD) have shifted research focus to earlier disease stages, necessitating more scalable approaches to identify cognitively unimpaired individuals with amyloid β (Aβ) pathology. Objective: To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying Aβ status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (Aβ positron emission tomography [PET] or cerebrospinal fluid [CSF]). Design, Setting, and Participants: This cross-sectional cohort study used data collected between June 2009 and March 2024. We included 2916 cognitively unimpaired participants from 12 international independent observational cohorts in the US, Europe, Australia, and Canada with available plasma p-tau217 levels and CSF or PET Aβ biomarkers. Performance comparisons between mass spectrometry and immunoassay-based p-tau217 measurements were also performed (n = 964). Exposures: Plasma p-tau217 levels measured by immunoassay. Main Outcome and Measures: Aβ status, determined by CSF or Aβ PET biomarkers. Results: Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were Aβ positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1 APOE ε4 allele. As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). I...