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

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

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)729-740
Number of pages12
JournalAnnals of neurology
Volume84
Issue number5
DOIs
StatePublished - Nov 1 2018

Fingerprint

Primary Progressive Aphasia
Amyloid
Pathology
Apolipoprotein E4
Positron-Emission Tomography
Cerebrospinal Fluid
Autopsy
Biomarkers
Apolipoproteins E
Semantics
Meta-Analysis
Alzheimer Disease
Genotype

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Bergeron, D., Gorno-Tempini, M. L., Rabinovici, G. D., Santos-Santos, M. A., Seeley, W., Miller, B. L., ... 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
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 ; Mesulam, Marek-Marsel ; Koric, Lejla ; Nora, Kristensen ; 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. / Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia. In: Annals of neurology. 2018 ; Vol. 84, No. 5. pp. 729-740.
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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.",
author = "David Bergeron and Gorno-Tempini, {Maria L.} and Rabinovici, {Gil D.} and Santos-Santos, {Miguel A.} and William Seeley and Miller, {Bruce L.} and Yolande Pijnenburg and Keulen, {M. Antoinette} and Colin Groot and {van Berckel}, {Bart N.M.} and {van der Flier}, {Wiesje M.} and Philip Scheltens and Rohrer, {Jonathan D.} and Warren, {Jason D.} and Schott, {Jonathan M.} and Fox, {Nick C.} and Raquel Sanchez-Valle and Oriol Grau-Rivera and Ellen Gelpi and Harro Seelaar and Papma, {Janne M.} and {van Swieten}, {John C.} and Hodges, {John R.} and Leyton, {Cristian E.} and Olivier Piguet and Emily Rogalski and Marek-Marsel Mesulam and Lejla Koric and Kristensen Nora and Je{\'e}re{\'e}mie Pariente and Bradford Dickerson and Mackenzie, {Ian R.} and Hsiung, {Ging Yuek R.} and Serge Belliard and Irwin, {David J.} and Wolk, {David A.} and Murray Grossman and Matthew Jones and Jennifer Harris and David Mann and Snowden, {Julie S.} and Patricio Chrem-Mendez and Calandri, {Ismael L.} and Amengual, {Alejandra A.} and Carole Miguet-Alfonsi and Eloi Magnin and Giuseppe Magnani and Roberto Santangelo and Vincent Deramecourt and Florence Pasquier and Niklas Mattsson and Christer Nilsson and Oskar Hansson and Julia Keith and Mario Masellis and Black, {Sandra E.} and Mat{\'i}as-Guiu, {Jordi A.} and Cabrera-Martin, {Mar{\'i}a Nieves} and Claire Paquet and Julien Dumurgier and Marc Teichmann and Marie Sarazin and Michel Bottlaender and Bruno Dubois and Rowe, {Christopher C.} and Villemagne, {Victor L.} and Rik Vandenberghe and Elias Granadillo and Edmond Teng and Mario Mendez and Meyer, {Philipp T.} and Lars Frings and Alberto Lle{\'o} and Rafael Blesa and Juan Fortea and Seo, {Sang Won} and Janine Diehl-Schmid and Timo Grimmer and Frederiksen, {Kristian Steen} and Pascual S{\'a}nchez-Juan and Ga{\"e}l Ch{\'e}telat and Willemijn Jansen and Bouchard, {R{\'e}mi W.} and Laforce, {Robert Jr} and Visser, {Pieter Jelle} and Rik Ossenkoppele",
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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, Seelaar, H, Papma, JM, van Swieten, JC, Hodges, JR, Leyton, CE, Piguet, O, Rogalski, E, Mesulam, M-M, Koric, L, Nora, K, Pariente, J, Dickerson, B, Mackenzie, IR, Hsiung, GYR, 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, MN, 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, SW, Diehl-Schmid, J, Grimmer, T, Frederiksen, KS, Sánchez-Juan, P, Chételat, G, Jansen, W, Bouchard, RW, Laforce, RJ, Visser, PJ & Ossenkoppele, R 2018, 'Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia', Annals of neurology, vol. 84, no. 5, pp. 729-740. https://doi.org/10.1002/ana.25333

Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia. / 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; Mesulam, Marek-Marsel; Koric, Lejla; Nora, Kristensen; 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.

In: Annals of neurology, Vol. 84, No. 5, 01.11.2018, p. 729-740.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia

AU - Bergeron, David

AU - Gorno-Tempini, Maria L.

AU - Rabinovici, Gil D.

AU - Santos-Santos, Miguel A.

AU - Seeley, William

AU - Miller, Bruce L.

AU - Pijnenburg, Yolande

AU - Keulen, M. Antoinette

AU - Groot, Colin

AU - van Berckel, Bart N.M.

AU - van der Flier, Wiesje M.

AU - Scheltens, Philip

AU - Rohrer, Jonathan D.

AU - Warren, Jason D.

AU - Schott, Jonathan M.

AU - Fox, Nick C.

AU - Sanchez-Valle, Raquel

AU - Grau-Rivera, Oriol

AU - Gelpi, Ellen

AU - Seelaar, Harro

AU - Papma, Janne M.

AU - van Swieten, John C.

AU - Hodges, John R.

AU - Leyton, Cristian E.

AU - Piguet, Olivier

AU - Rogalski, Emily

AU - Mesulam, Marek-Marsel

AU - Koric, Lejla

AU - Nora, Kristensen

AU - Pariente, Jeéreémie

AU - Dickerson, Bradford

AU - Mackenzie, Ian R.

AU - Hsiung, Ging Yuek R.

AU - Belliard, Serge

AU - Irwin, David J.

AU - Wolk, David A.

AU - Grossman, Murray

AU - Jones, Matthew

AU - Harris, Jennifer

AU - Mann, David

AU - Snowden, Julie S.

AU - Chrem-Mendez, Patricio

AU - Calandri, Ismael L.

AU - Amengual, Alejandra A.

AU - Miguet-Alfonsi, Carole

AU - Magnin, Eloi

AU - Magnani, Giuseppe

AU - Santangelo, Roberto

AU - Deramecourt, Vincent

AU - Pasquier, Florence

AU - Mattsson, Niklas

AU - Nilsson, Christer

AU - Hansson, Oskar

AU - Keith, Julia

AU - Masellis, Mario

AU - Black, Sandra E.

AU - Matías-Guiu, Jordi A.

AU - Cabrera-Martin, María Nieves

AU - Paquet, Claire

AU - Dumurgier, Julien

AU - Teichmann, Marc

AU - Sarazin, Marie

AU - Bottlaender, Michel

AU - Dubois, Bruno

AU - Rowe, Christopher C.

AU - Villemagne, Victor L.

AU - Vandenberghe, Rik

AU - Granadillo, Elias

AU - Teng, Edmond

AU - Mendez, Mario

AU - Meyer, Philipp T.

AU - Frings, Lars

AU - Lleó, Alberto

AU - Blesa, Rafael

AU - Fortea, Juan

AU - Seo, Sang Won

AU - Diehl-Schmid, Janine

AU - Grimmer, Timo

AU - Frederiksen, Kristian Steen

AU - Sánchez-Juan, Pascual

AU - Chételat, Gaël

AU - Jansen, Willemijn

AU - Bouchard, Rémi W.

AU - Laforce, Robert Jr

AU - Visser, Pieter Jelle

AU - Ossenkoppele, Rik

PY - 2018/11/1

Y1 - 2018/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85056802535&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056802535&partnerID=8YFLogxK

U2 - 10.1002/ana.25333

DO - 10.1002/ana.25333

M3 - Article

C2 - 30255971

AN - SCOPUS:85056802535

VL - 84

SP - 729

EP - 740

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 5

ER -

Bergeron D, Gorno-Tempini ML, Rabinovici GD, Santos-Santos MA, Seeley W, Miller BL et al. Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia. Annals of neurology. 2018 Nov 1;84(5):729-740. https://doi.org/10.1002/ana.25333