Prevalence of amyloid-β 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, Jeéreémie 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. Matías-Guiu, María-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 Lleó, Rafael Blesa, Juan Fortea, Sang Won Seo, Janine Diehl-Schmid, Timo Grimmer, Kristian Steen Frederiksen, Pascual Sánchez-Juan, Gaël Chételat, Willemijn Jansen, R. mi W. Bouchard, Robert Jr Laforce, Pieter Jelle Visser, Rik Ossenkoppele

Research output: Contribution to journalArticleAcademicpeer-review


OBJECTIVE: To estimate the prevalence of amyloid-positivity, defined by PET/CSF biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants.

METHODS: We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n=443], non-fluent [nfvPPA, n=333], semantic [svPPA, n=401] and mixed/unclassifiable [PPA-M/U, n=74] variants of PPA) from 36 centers, with a measure of amyloid-β 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) ε4 status was determined using generalized estimating equation models.

RESULTS: Amyloid-β positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%) (p<0.001). Prevalence of amyloid-β positivity increased with age in nfvPPA (from 10% at age 50 to 27% at age 80, p<0.01) and svPPA (from 6% at age 50 to 32% at age 80, p<0.001), but not in lvPPA (p=0.94). Across PPA variants, APOE ε4 carriers were more often amyloid-β positive (58.0%) than non-carriers (35.0%, p<0.001). Autopsy data revealed Alzheimer's disease (AD) 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%).

INTERPRETATION: 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 taken into account when interpreting Aβ biomarkers in PPA patients. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)729-740
JournalAnnals of Neurology
Issue number5
Early online date26 Sep 2018
Publication statusPublished - 2018

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