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

TitlePrevalence of amyloid-β pathology in distinct variants of primary progressive aphasia.
Publication TypeJournal Article
Year of Publication2018
AuthorsBergeron, D, Gorno-Tempini, ML, Rabinovici, GD, Santos-Santos, MA, Seeley, W, Miller, BL, Pijnenburg, Y, M Keulen, A, 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, Seelaar, H, Papma, JM, van Swieten, JC, Hodges, JR, Leyton, CE, Piguet, O, Rogalski, EJ, Mesulam, MM, Koric, L, Nora, K, Pariente, J, Dickerson, B, Mackenzie, IR, Hsiung, G-YR, Belliard, S, Irwin, DJ, Wolk, DA, Grossman, M, Jones, M, Harris, J, Mann, D, Snowden, JS, Chrem-Mendez, P, Calandri, IL, Amengual, AA, Miguet-Alfonsi, C, Magnin, E, Magnani, G, Santangelo, R, Deramecourt, V, Pasquier, F, Mattsson, N, Nilsson, C, Hansson, O, Keith, J, Masellis, M, Black, SE, Matías-Guiu, JA, Cabrera-Martin, M-N, Paquet, C, Dumurgier, J, Teichmann, M, Sarazin, M, Bottlaender, M, Dubois, B, Rowe, CC, Villemagne, VL, Vandenberghe, R, Granadillo, E, Teng, E, Mendez, M, Meyer, PT, Frings, L, Lleó, A, Blesa, R, Fortea, J, Seo, SWon, Diehl-Schmid, J, Grimmer, T, Frederiksen, KSteen, Sánchez-Juan, P, Chetelat, G, Jansen, W, Bouchard, RW, Laforce, Jr, R, Visser, PJelle, Ossenkoppele, R
JournalAnn Neurol
Date Published2018 Nov

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.

Alternate JournalAnn. Neurol.
PubMed ID30255971
Grant ListP50 AG023501 / AG / NIA NIH HHS / United States
U01 AG052943 / AG / NIA NIH HHS / United States
P01 AG019724 / AG / NIA NIH HHS / United States
R01 NS100440 / NS / NINDS NIH HHS / United States
R01 NS050915 / NS / NINDS NIH HHS / United States
U54 NS092089 / NS / NINDS NIH HHS / United States
K24 DC015544 / DC / NIDCD NIH HHS / United States
/ / Canadian Institutes of Health Research /