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 Seelaar & 66 others JM 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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Primary Progressive Aphasia
Amyloid
Pathology
Apolipoprotein E4
Positron-Emission Tomography
Cerebrospinal Fluid
Autopsy
Biomarkers
Apolipoproteins E
Semantics
Meta-Analysis
Alzheimer Disease
Genotype

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Bergeron, D., Gorno-Tempini, ML., Rabinovici, GD., Santos-Santos, MA., Seeley, W., Miller, BL., ... 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

Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia. / 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, EJ; Mesulam, MM; 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, Roberto; 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; Steen Frederiksen, K; Sánchez-Juan, P; Chételat, G; Jansen, W; Bouchard, RW; Laforce, RJ; Visser, PJ; Ossenkoppele, R.

In: Annals of Neurology, Vol. 84, No. 5, 2018, p. 729-740.

Research output: Contribution to journalArticle

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, EJ, Mesulam, MM, 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, Steen Frederiksen, K, 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
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;84(5):729-740. https://doi.org/10.1002/ana.25333
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, EJ ; Mesulam, MM ; 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, Roberto ; 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 ; Steen Frederiksen, K ; Sánchez-Juan, P ; Chételat, G ; Jansen, W ; Bouchard, RW ; Laforce, RJ ; Visser, PJ ; Ossenkoppele, R. / 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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title = "Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia",
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. {\circledC} 2018 American Neurological Association",
author = "D Bergeron and ML Gorno-Tempini and GD Rabinovici and MA Santos-Santos and W Seeley and BL Miller and Y Pijnenburg and MA Keulen and C Groot and {van Berckel}, BNM and {van der Flier}, WM and P Scheltens and JD Rohrer and JD Warren and JM Schott and NC Fox and R Sanchez-Valle and O Grau-Rivera and E Gelpi and H Seelaar and JM Papma and {van Swieten}, JC and JR Hodges and CE Leyton and O Piguet and EJ Rogalski and MM Mesulam and L Koric and K Nora and J Pariente and B Dickerson and IR Mackenzie and GYR Hsiung and S Belliard and DJ Irwin and DA Wolk and M Grossman and M Jones and J Harris and D Mann and JS Snowden and P Chrem-Mendez and IL Calandri and AA Amengual and C Miguet-Alfonsi and E Magnin and G Magnani and Roberto Santangelo and V Deramecourt and F Pasquier and N Mattsson and C Nilsson and O Hansson and J Keith and M Masellis and SE Black and JA Mat{\'i}as-Guiu and MN Cabrera-Martin and C Paquet and J Dumurgier and M Teichmann and M Sarazin and M Bottlaender and B Dubois and CC Rowe and VL Villemagne and R Vandenberghe and E Granadillo and E Teng and M Mendez and PT Meyer and L Frings and A Lle{\'o} and R Blesa and J Fortea and SW Seo and J Diehl-Schmid and T Grimmer and {Steen Frederiksen}, K and P S{\'a}nchez-Juan and G Ch{\'e}telat and W Jansen and RW Bouchard and RJ Laforce and PJ Visser and R Ossenkoppele",
year = "2018",
doi = "10.1002/ana.25333",
language = "English",
volume = "84",
pages = "729--740",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
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}

TY - JOUR

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

AU - Bergeron, D

AU - Gorno-Tempini, ML

AU - Rabinovici, GD

AU - Santos-Santos, MA

AU - Seeley, W

AU - Miller, BL

AU - Pijnenburg, Y

AU - Keulen, MA

AU - Groot, C

AU - van Berckel, BNM

AU - van der Flier, WM

AU - Scheltens, P

AU - Rohrer, JD

AU - Warren, JD

AU - Schott, JM

AU - Fox, NC

AU - Sanchez-Valle, R

AU - Grau-Rivera, O

AU - Gelpi, E

AU - Seelaar, H

AU - Papma, JM

AU - van Swieten, JC

AU - Hodges, JR

AU - Leyton, CE

AU - Piguet, O

AU - Rogalski, EJ

AU - Mesulam, MM

AU - Koric, L

AU - Nora, K

AU - Pariente, J

AU - Dickerson, B

AU - Mackenzie, IR

AU - Hsiung, GYR

AU - Belliard, S

AU - Irwin, DJ

AU - Wolk, DA

AU - Grossman, M

AU - Jones, M

AU - Harris, J

AU - Mann, D

AU - Snowden, JS

AU - Chrem-Mendez, P

AU - Calandri, IL

AU - Amengual, AA

AU - Miguet-Alfonsi, C

AU - Magnin, E

AU - Magnani, G

AU - Santangelo, Roberto

AU - Deramecourt, V

AU - Pasquier, F

AU - Mattsson, N

AU - Nilsson, C

AU - Hansson, O

AU - Keith, J

AU - Masellis, M

AU - Black, SE

AU - Matías-Guiu, JA

AU - Cabrera-Martin, MN

AU - Paquet, C

AU - Dumurgier, J

AU - Teichmann, M

AU - Sarazin, M

AU - Bottlaender, M

AU - Dubois, B

AU - Rowe, CC

AU - Villemagne, VL

AU - Vandenberghe, R

AU - Granadillo, E

AU - Teng, E

AU - Mendez, M

AU - Meyer, PT

AU - Frings, L

AU - Lleó, A

AU - Blesa, R

AU - Fortea, J

AU - Seo, SW

AU - Diehl-Schmid, J

AU - Grimmer, T

AU - Steen Frederiksen, K

AU - Sánchez-Juan, P

AU - Chételat, G

AU - Jansen, W

AU - Bouchard, RW

AU - Laforce, RJ

AU - Visser, PJ

AU - Ossenkoppele, R

PY - 2018

Y1 - 2018

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. © 2018 American Neurological Association

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. © 2018 American Neurological Association

U2 - 10.1002/ana.25333

DO - 10.1002/ana.25333

M3 - Article

VL - 84

SP - 729

EP - 740

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 5

ER -