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

D Bergeron, ML Gorno-Tempini, GD Rabinovici, MA Santos-Santos, W Seeley, BL Miller, Y Pijnenburg, MA Keulen, C Groot, BNM van Berckel, WM van der Flier, P Scheltens, JD Rohrer, JD Warren, JM Schott, NC Fox, R Sanchez-Valle, O Grau-Rivera, E Gelpi, H SeelaarJM Papma, JC van Swieten, JR Hodges, CE Leyton, O Piguet, EJ Rogalski, MM Mesulam, L Koric, K Nora, J Pariente, B Dickerson, IR Mackenzie, GYR Hsiung, S Belliard, DJ Irwin, DA Wolk, M Grossman, M Jones, J Harris, D Mann, JS Snowden, P Chrem-Mendez, IL Calandri, AA Amengual, C Miguet-Alfonsi, E Magnin, G Magnani, Roberto Santangelo, V Deramecourt, F Pasquier, N Mattsson, C Nilsson, O Hansson, J Keith, M Masellis, SE Black, JA Matías-Guiu, MN Cabrera-Martin, C Paquet, J Dumurgier, M Teichmann, M Sarazin, M Bottlaender, B Dubois, CC Rowe, VL Villemagne, R Vandenberghe, E Granadillo, E Teng, M Mendez, PT Meyer, L Frings, A Lleó, R Blesa, J Fortea, SW Seo, J Diehl-Schmid, T Grimmer, K Steen Frederiksen, P Sánchez-Juan, G Chételat, W Jansen, RW Bouchard, RJ Laforce, PJ Visser, R Ossenkoppele

Research output: Contribution to journalArticle

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. © 2018 American Neurological Association
Original languageEnglish
Pages (from-to)729-740
Number of pages12
JournalAnnals of Neurology
Volume84
Issue number5
DOIs
Publication statusPublished - 2018

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    Bergeron, D., Gorno-Tempini, ML., Rabinovici, GD., Santos-Santos, MA., Seeley, W., Miller, BL., Pijnenburg, Y., Keulen, MA., Groot, C., van Berckel, BNM., van der Flier, WM., Scheltens, P., Rohrer, JD., Warren, JD., Schott, JM., Fox, NC., Sanchez-Valle, R., Grau-Rivera, O., Gelpi, E., ... Ossenkoppele, R. (2018). Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia. Annals of Neurology, 84(5), 729-740. https://doi.org/10.1002/ana.25333