Prevalence of amyloid-beta pathology in distinct variants of primary progressive aphasia

David Bergeron*, Maria L. Gorno-Tempini, Gil D. Rabinovici, Miguel A. Santos-Santos, William Seeley, Bruce L. Miller, Yolande Pijnenburg, M. Antoinette Keulen, Colin Groot, Bart N. M. van Berckel, Wiesje M. van der Flier, Philip Scheltens, Jonathan D. Rohrer, Jason D. Warren, Jonathan M. Schott, Nick C. Fox, Raquel Sanchez-Valle, Oriol Grau-Rivera, Ellen Gelpi, Harro SeelaarJanne M. Papma, John C. van Swieten, John R. Hodges, Cristian E. Leyton, Olivier Piguet, Emily J. Rogalski, Marsel M. Mesulam, Lejla Koric, Kristensen Nora, Jeereemie Pariente, Bradford Dickerson, Ian R. Mackenzie, Ging-Yuek R. Hsiung, Serge Belliard, David J. Irwin, David A. Wolk, Murray Grossman, Matthew Jones, Jennifer Harris, David Mann, Julie S. Snowden, Patricio Chrem-Mendez, Ismael L. Calandri, Alejandra A. Amengual, Carole Miguet-Alfonsi, Eloi Magnin, Giuseppe Magnani, Roberto Santangelo, Vincent Deramecourt, Florence Pasquier, Niklas Mattsson, Christer Nilsson, Oskar Hansson, Julia Keith, Mario Masellis, Sandra E. Black, Jordi A. Matias-Guiu, Maria-Nieves Cabrera-Martin, Claire Paquet, Julien Dumurgier, Marc Teichmann, Marie Sarazin, Michel Bottlaender, Bruno Dubois, Christopher C. Rowe, Victor L. Villemagne, Rik Vandenberghe, Elias Granadillo, Edmond Teng, Mario Mendez, Philipp T. Meyer, Lars Frings, Alberto Lleo, Rafael Blesa, Juan Fortea, Sang Won Seo, Janine Diehl-Schmid, Timo Grimmer, Kristian Steen Frederiksen, Pascual Sanchez-Juan, Gael Chetelat, Willemijn Jansen, Remi W. Bouchard, Robert Jr. Laforce, Pieter Jelle Visser, Rik Ossenkoppele

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objective Methods To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebrospinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants. We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid-beta pathology (CSF [n = 600], PET [n = 366], and/or autopsy [n = 378]) available. The estimated prevalence of amyloid positivity according to PPA variant, age, and apolipoprotein E (ApoE) epsilon 4 status was determined using generalized estimating equation models. Results Interpretation Amyloid-beta positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%; p <0.001). Prevalence of amyloid-beta positivity increased with age in nfvPPA (from 10% at age 50 years to 27% at age 80 years, p <0.01) and svPPA (from 6% at age 50 years to 32% at age 80 years, p <0.001), but not in lvPPA (p = 0.94). Across PPA variants, ApoE epsilon 4 carriers were more often amyloid-beta positive (58.0%) than noncarriers (35.0%, p <0.001). Autopsy data revealed Alzheimer disease pathology as the most common pathologic diagnosis in lvPPA (76%), frontotemporal lobar degeneration-TDP-43 in svPPA (80%), and frontotemporal lobar degeneration-TDP-43/tau in nfvPPA (64%). This study shows that the current PPA classification system helps to predict underlying pathology across different cohorts and clinical settings, and suggests that age and ApoE genotype should be considered when interpreting amyloid-beta biomarkers in PPA patients. Ann Neurol 2018;84:737-748

Original languageEnglish
Pages (from-to)729-740
Number of pages12
JournalAnnals of Neurology
Issue number5
Publication statusPublished - Nov 2018


  • PET

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