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Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia

David Bergeron 1, 2 Maria Gorno-Tempini 3 Gil Rabinovici 3 Miguel Santos-Santos 3, 4 William Seeley 3 Bruce Miller 3 Yolande Pijnenburg 2 M Antoinette Keulen 2 Colin Groot 2 Bart van Berckel 5 Wiesje van der Flier 2 Philip Scheltens 2 Jonathan Rohrer 6 Jason Warren 6 Jonathan Schott 6 Nick Fox 6 Raquel Sánchez-Valle 7 Oriol Grau-Rivera 7 Ellen Gelpi 7, 8 Harro Seelaar 9 Janne Papma 9 John van Swieten 9 John Hodges 10, 11, 12 Cristian Leyton 13, 14 Olivier Piguet 10, 11, 12 Emily Rogalski 15, 16 Marsel Mesulam 16 Lejla Koric 17 Kristensen Nora 17 Jeéreémie Pariente 18 Bradford Dickerson 13, 14 Ian Mackenzie 19 Ging-Yuek Hsiung 19 Serge Belliard 19 David Irwin 20 David Wolk 20 Murray Grossman 20 Matthew Jones 21, 22 Jennifer Harris 22 David Mann 22 Julie Snowden 22 Patricio Chrem-Mendez 23 Ismael Calandri 23 Alejandra Amengual 23 Carole Miguet-Alfonsi 24 Eloi Magnin 24 Giuseppe Magnani 25, 26 Roberto Santangelo 25, 26 Vincent Deramecourt 27 Florence Pasquier 27 Niklas Mattsson 28 Christer Nilsson 28 Oskar Hansson 28, 29 Julia Keith 30 Mario Masellis 31, 30 Sandra Black 31, 30 Jordi Matías-Guiu 32, 33 María-Nieves Cabrera-Martin 32, 33 Claire Paquet 34 Julien Dumurgier 34 Marc Teichmann 35 Marie Sarazin 36 Michel Bottlaender 36 Bruno Dubois 35 Christopher Rowe 37, 38 Victor Villemagne 37, 38 Rik Vandenberghe 39 Elias Granadillo 40, 41 Edmond Teng 40 Mario Mendez 42 Philipp Meyer 43 Lars Frings 43 Alberto Lleó 44, 45, 46 Rafael Blesa 44, 45 Juan Fortea 44, 45 Sang Won Seo 47 Janine Diehl-Schmid 48 Timo Grimmer 48 Kristian Steen Frederiksen 49 Pascual Sánchez-Juan 50 Gaël Chételat 51 Willemijn Jansen 52, 53 Rémi Bouchard 1 Robert Jr Laforce 1, 54 Pieter Jelle Visser 4, 52 Rik Ossenkoppele 55, 28
1 Interdisciplinary Clinic of Memory of the Child Jesus
2 Alzheimer center Amsterdam
3 Memory and Aging Center [San Francisco, CA, États-Unis]
4 Llobregat Hospital [Barcelona]
5 VU University Medical Center [Amsterdam]
6 Institute of Neurology [London]
7 August Pi i Sunyer Biomedical Research Institute [Barcelona]
8 Medizinische Universität Wien = Medical University of Vienna
9 Erasmus MC - Erasmus University Medical Center [Rotterdam]
10 The University of Sydney
11 UNSW - University of New South Wales [Sydney]
12 Australian Research Council Centre of Excellence in Cognition and its Disorders [Sidney]
13 Massachusetts Alzheimer's Disease Research Center
14 HMS - Harvard Medical School [Boston]
15 Rush University [Chicago]
16 Northwestern University Medical School [Chicago]
17 Service de neurologie et de neuropsychologie
18 ToNIC - Toulouse Neuro Imaging Center
19 UBC - University of British Columbia
20 University of Pennsylvania [Philadelphia]
21 Greater Manchester Neurosciences Centre
22 University of Manchester [Manchester]
23 Neurological Research Institute [Buenos Aires]
24 CHRU Besançon - Centre Hospitalier Régional Universitaire [Besançon]
25 Vita Salute University [Milan]
26 IRCCS Ospedale San Raffaele [Milan, Italy]
27 U1171 - Troubles cognitifs dégénératifs et vasculaires
28 Lund University [Lund]
29 Skane University Hospital [Malmo]
30 University of Toronto
31 SRI - Sunnybrook Research Institute [Toronto]
32 UCM - Complutense University of Madrid
33 San Carlos Clinical Hospital [Madrid]
34 Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
35 CHU Pitié-Salpêtrière [AP-HP]
36 IMIV - U1023 - ERL9218 - Imagerie Moléculaire in Vivo
37 Austin Health
38 University of Melbourne
39 University Hospitals Leuven [Leuven]
40 UCLA - University of California [Los Angeles]
41 VA Greater Los Angeles Healthcare System
42 West Los Angeles VA Medical Center
43 University Hospital of Freiburg
44 UAB - Universitat Autònoma de Barcelona [Barcelona]
45 Santa Cruz and Saint Paul Hospital [Barcelona]
46 Center for Biomedical Network Research on Neurodegenerative Diseases [Barcelona]
47 Samsung Medical Center Sungkyunkwan University School of Medicine
48 TUM - Technical University of Munich
49 Danish Dementia Research Center [Copenhagen]
50 Marqués de Valdecilla University Hospital [Santander]
51 PhIND - Physiopathologie et imagerie des troubles neurologiques
52 MUMC - School for Mental Health and Neuroscience - Alzheimer Center Limburg
53 Banner Alzheimer's Institute [Phoenix]
54 Clinique Interdisciplinaire de Mémoire de l'Enfant-Jésus
55 VU University Amsterdam
Abstract : Objective: 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. Methods: 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-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 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 ε4 carriers were more often amyloid-β 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%). 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 considered when interpreting amyloid-β biomarkers in PPA patients. Ann Neurol 2018;84:737-748.
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Journal articles
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https://www.hal.inserm.fr/inserm-02749861
Contributor : Nathalie Duchange <>
Submitted on : Wednesday, June 3, 2020 - 4:14:37 PM
Last modification on : Thursday, August 20, 2020 - 5:11:37 PM

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CEA | CEA-UPSAY | JOLIOT | COMUE-NORMANDIE | SHFJ | CEA-DRF | UNIV-LILLE | UNIV-AMU | UNICAEN | UNIV-PARIS-SACLAY | CNRS | UNIV-TLSE3

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David Bergeron, Maria Gorno-Tempini, Gil Rabinovici, Miguel Santos-Santos, William Seeley, et al.. Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia. Annals of Neurology, Wiley, 2018, 84 (5), pp.729-740. ⟨10.1002/ana.25333⟩. ⟨inserm-02749861⟩

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