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