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 Seelaar; Janne M Papma; John C van Swieten; John R Hodges; Cristian E Leyton; Olivier Piguet; Emily J Rogalsky; Marsel M Mesulam; Lejla Koric; Kristensen Nora; Jérémie 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 Dumuirger; 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; Laforce Robert; Pieter Jelle Visser; Rik Ossenkoppele

doi:10.1002/ana.25333

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 J Rogalsky, Marsel M Mesulam, Lejla Koric, Kristensen Nora, Jérémie 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 Dumuirger, 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, Laforce Robert, Pieter Jelle Visser, Rik Ossenkoppele

Department of Neurology

176 Citations (Scopus)

Abstract

OBJECTIVE: To estimate the prevalence of amyloid-positivity, defined by PET/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], non-fluent [nfvPPA, n=333], semantic [svPPA, n=401] and mixed/unclassifiable [PPA-M/U, 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 to 27% at age 80, p<0.01) and svPPA (from 6% at age 50 to 32% at age 80, 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 non-carriers (35.0%, p<0.001). Autopsy data revealed Alzheimer's disease (AD) 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 taken into account when interpreting Aβ biomarkers in PPA patients. This article is protected by copyright. All rights reserved.

Original language	English
Journal	Annals of Neurology
Volume	84
Issue number	5
Pages (from-to)	729-740
ISSN	0364-5134
DOIs	https://doi.org/10.1002/ana.25333
Publication status	Published - Nov 2018

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Bergeron, D., Gorno-Tempini, M. L., Rabinovici, G. D., Santos-Santos, M. A., Seeley, W., Miller, B. L., Pijnenburg, Y., Keulen, M. A., Groot, C., van Berckel, B. N. M., van der Flier, W. M., Scheltens, P., Rohrer, J. D., Warren, J. D., Schott, J. M., Fox, N. C., 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

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, Rogalsky, 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, Dumuirger, 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, Robert, L, 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

@article{b9698bfe00db401b9ef0a5db963dd765,

title = "Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia",

abstract = "OBJECTIVE: To estimate the prevalence of amyloid-positivity, defined by PET/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], non-fluent [nfvPPA, n=333], semantic [svPPA, n=401] and mixed/unclassifiable [PPA-M/U, 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 to 27\% at age 80, p<0.01) and svPPA (from 6\% at age 50 to 32\% at age 80, 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 non-carriers (35.0\%, p<0.001). Autopsy data revealed Alzheimer's disease (AD) 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 taken into account when interpreting Aβ biomarkers in PPA patients. This article is protected by copyright. All rights reserved.",

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 Rogalsky, \{Emily J\} and Mesulam, \{Marsel M\} and Lejla Koric and Kristensen Nora and J{\'e}r{\'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 Mar{\'i}a-Nieves Cabrera-Martin and Claire Paquet and Julien Dumuirger 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 and Visser, \{Pieter Jelle\} and Rik Ossenkoppele",

year = "2018",

month = nov,

doi = "10.1002/ana.25333",

language = "English",

volume = "84",

pages = "729--740",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley \& Sons Inc.",

number = "5",

}

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 - Rogalsky, Emily J

AU - Mesulam, Marsel M

AU - Koric, Lejla

AU - Nora, Kristensen

AU - Pariente, Jérémie

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 - Dumuirger, 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 - Robert, Laforce

AU - Visser, Pieter Jelle

AU - Ossenkoppele, Rik

PY - 2018/11

Y1 - 2018/11

N2 - OBJECTIVE: To estimate the prevalence of amyloid-positivity, defined by PET/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], non-fluent [nfvPPA, n=333], semantic [svPPA, n=401] and mixed/unclassifiable [PPA-M/U, 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 to 27% at age 80, p<0.01) and svPPA (from 6% at age 50 to 32% at age 80, 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 non-carriers (35.0%, p<0.001). Autopsy data revealed Alzheimer's disease (AD) 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 taken into account when interpreting Aβ biomarkers in PPA patients. This article is protected by copyright. All rights reserved.

AB - OBJECTIVE: To estimate the prevalence of amyloid-positivity, defined by PET/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], non-fluent [nfvPPA, n=333], semantic [svPPA, n=401] and mixed/unclassifiable [PPA-M/U, 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 to 27% at age 80, p<0.01) and svPPA (from 6% at age 50 to 32% at age 80, 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 non-carriers (35.0%, p<0.001). Autopsy data revealed Alzheimer's disease (AD) 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 taken into account when interpreting Aβ biomarkers in PPA patients. This article is protected by copyright. All rights reserved.

UR - https://www.scopus.com/pages/publications/85056802535

U2 - 10.1002/ana.25333

DO - 10.1002/ana.25333

M3 - Journal article

C2 - 30255971

SN - 0364-5134

VL - 84

SP - 729

EP - 740

JO - Annals of Neurology

JF - Annals of Neurology

IS - 5

ER -

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

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