Journal articles

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

David Bergeron ^{1, 2} Maria L Gorno-Tempini ³ Gil D Rabinovici ³ Miguel A Santos-Santos ^{3, 4} William Seeley ³ Bruce L Miller ³ yolande Pijnenburg ² M Antoinette Keulen ² Colin Groot ² Bart N.M. van Berckel ⁵ Wiesje M van Der Flier ² Philip Scheltens ² Jonathan D Rohrer ⁶ Jason D Warren ⁶ Jonathan M Schott ⁶ Nick C Fox ⁶ Raquel Sánchez-Valle ⁷ Oriol Grau-Rivera ⁷ Ellen Gelpi ^{7, 8} Harro Seelaar ⁹ Janne M Papma ⁹ John C van Swieten ⁹ John R Hodges ^{10, 11, 12} Cristian E Leyton ^{13, 14} Olivier Piguet ^{10, 11, 12} Emily J Rogalski ^{15, 16} Marsel M Mesulam ¹⁶ Lejla Koric ¹⁷ Kristensen Nora ¹⁷ Jeéreémie Pariente ¹⁸ Bradford Dickerson ^{13, 14} Ian R Mackenzie ¹⁹ Ging-yuek R Hsiung ¹⁹ Serge Belliard ¹⁹ David J Irwin ²⁰ David A Wolk ²⁰ Murray Grossman ²⁰ Matthew Jones ^{21, 22} Jennifer Harris ²² David Mann ²² Julie S Snowden ²² Patricio Chrem-Mendez ²³ Ismael L Calandri ²³ Alejandra A 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 E Black ^{31, 30} Jordi A 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 C. Rowe ^{37, 38} Victor L. Villemagne ^{37, 38} Rik Vandenberghe ³⁹ Elias Granadillo ^{40, 41} Edmond Teng ⁴⁰ Mario Mendez ⁴² Philipp T 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 W 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 de Besançon

25 Vita Salute University [Milan]

26 IRCCS Ospedale San Raffaele [Milan, Italy]

27 TCDV - Troubles cognitifs dégénératifs et vasculaires - U 1171

28 Lund University [Lund]

29 Skane University Hospital [Malmo]

30 University of Toronto

31 SRI - Sunnybrook Research Institute [Toronto]

32 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [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

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 - Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne]

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 - Vrije universiteit = Free university of Amsterdam [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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Neurons and Cognition [q-bio.NC]

Complete list of metadata

https://www.hal.inserm.fr/inserm-02749861
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Submitted on : Wednesday, June 3, 2020 - 4:14:37 PM
Last modification on : Wednesday, June 1, 2022 - 3:58:12 AM