Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex

Rik Ossenkoppele, Emma M. Coomans, Liana G. Apostolova, Suzanne L. Baker, Henryk Barthel, Thomas G. Beach, Tammie L.S. Benzinger, Tobey J. Betthauser, Gérard N. Bischof, Michel Bottlaender, Pierrick Bourgeat, Anouk den Braber, Matthias Brendel, Adam M. Brickman, David M. Cash, María C. Carrillo, William Coath, Bradley T. Christian, Bradford C. Dickerson, Vincent Doré, Alexander Drzezga, Azadeh Feizpour, Wiesje M. van der Flier, Nicolai Franzmeier, Giovanni B. Frisoni, Valentina Garibotto, Elsmarieke van de Giessen, Juan Domingo-Gispert, Johannes Gnörich, Yuna Gu, Yihui Guan, Bernard Hanseeuw, Theresa M. Harrison, Clifford R. Jack, Elena Jaeger, William J. Jagust, Willemijn J. Jansen, Renaud La Joie, Keith A. Johnson, Sterling C. Johnson, Ian Kennedy, Jun Pyo Kim, Koen Van Laere, Julien Lagarde, Patrick J. Lao, José A. Luchsinger, Silke Kern, William Charles Kreisl, Vincent Malotaux, Maura Malpetti, Jennifer J. Manly, Xiaoxie Mao, Niklas Mattsson, Ronald C. Petersen, Konstantin Messerschmidt, Carolina Minguillón, Elizabeth C. Mormino, John T. O’Brien, Sebastian Palmqvist, Débora Elisa Peretti, Ronald C. Petersen, Yolande A.L. Pijnenburg, Michael J. Pontecorvo, Judes Poirier, Gil D. Rabinovici, Nesrine Rahmouni, Shannon L. Risacher, Pedro Rosa‐Neto, Howard Rosen, Christopher C. Rowe, James B. Rowe, Michael Rullmann, Yasmine Salman, Marie Sarazin, Andrew J. Saykin, Julie A. Schneider, Michael Schöll, Jonathan M. Schott, Sang Won Seo, Geidy E. Serrano, Sergey Shcherbinin, Mahnaz Shekari, Ingmar Skoog, Ruben Smith, Reisa A. Sperling, Laure Spruyt, Erik Stomrud, Olof Strandberg, Joseph Therriault, Fang Xie, Rik Vandenberghe, Victor L. Villemagne, Sylvia Villeneuve, Pieter Jelle Visser, Hillary Vossler, Christina B. Young, Colin Groot, Oskar Hansson

Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia. We found that from age 60 years to 80 years, tau PET positivity in a temporal composite region increased from 1.1% to 4.4% among CU amyloid-β (Aβ)-negative participants and from 17.4% to 22.2% among CU Aβ-positive participants. Across the same age span, tau PET positivity decreased from 68.0% to 52.9% in participants with MCI and from 91.5% to 74.6% in participants with dementia. Age, Aβ status, APOE ε4 carriership and female sex were all associated with a higher prevalence of tau PET positivity across groups. APOE ε4 carriership in CU individuals lowered the age at onset of both Aβ positivity and tau positivity by decades. Finally, we replicated these associations in an independent autopsy dataset (N = 5,072 from 3 cohorts).