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Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia
Open accessAbstract
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
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“However, ADNC is observed not only in individuals with the typical, amnestic clinical presentation but also in people with atypical, non‐amnestic presentations.”
From Automatic classification of AD pathology in FTD phenotypes using natural speech (2024) · cites this paper as [13]
Experimental — accuracy not yet measuredIn the citing paper
“Alternatively, lesions of the Alzheimer type are frequently observed as copathology in post-mortem examination of people who had other neurodegenerative diseases.40,41,94,96”
From Clinical diagnosis of Alzheimer’s disease: Recommendations of the International Working Group (2021) · cites this paper as [94]
In the citing paper
“Other phenotypes, including the behavioural variant or dysexecutive variant,95,96 the corticobasal variant,97,98 and the other variants of primary progressive aphasia94,99 (appendix p 2), are less commonly related to Alzheimer’s disease pathology (uncommon Alzheimer’s disease phenotypes).”
From Clinical diagnosis of Alzheimer’s disease: Recommendations of the International Working Group (2021) · cites this paper as [94]
In the citing paper
“This biomarker positivity is particularly ambiguous in the case of behavioural or dysexecutive variants, corticobasal syndrome, and semantic or non-fluent variants of primary progressive aphasia, in which the presence of positive Alzheimer’s disease biomarkers can be considered either as Alzheimer’s disease copathology or atypical forms of Alzheimer’s disease94,96,98,99 (appendix p 2).”
From Clinical diagnosis of Alzheimer’s disease: Recommendations of the International Working Group (2021) · cites this paper as [94]
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Metadata
- Authors
- 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., Seelaar, H., Papma, J. M., van Swieten, J. C., Hodges, J. R., Leyton, C. E., Piguet, O., Rogalski, E. J., Mesulam, M. M., Koric, L., Kristensen, N., Pariente, J., Dickerson, B., Mackenzie, I. R., Hsiung, G. R., Belliard, S., Irwin, D. J., Wolk, D. A., Grossman, M., Jones, M., Harris, J., Mann, D., Snowden, J. S., Chrem‐Mendez, P., Calandri, I. L., Amengual, A. A., Miguet‐Alfonsi, C., Magnin, E., Magnani, G., Santangelo, R., Deramecourt, V., Pasquier, F., Mattsson, N., Nilsson, C., Hansson, O., Keith, J., Masellis, M., Black, S. E., Matías‐Guiu, J. A., Cabrera‐Martin, M., Paquet, C., Dumurgier, J., Teichmann, M., Sarazin, M., Bottlaender, M., Dubois, B., Rowe, C. C., Villemagne, V. L., Vandenberghe, R., Granadillo, E., Teng, E., Mendez, M., Meyer, P. T., Frings, L., Lleó, A., Blesa, R., Fortea, J., Seo, S. W., Diehl‐Schmid, J., Grimmer, T., Frederiksen, K. S., Sánchez‐Juan, P., Chételat, G., Jansen, W., Bouchard, R. W., Laforce, R. J., Visser, P. J., & Ossenkoppele, R.
- Affiliations
- Amsterdam Neuroscience (NL)
- University of California, San Francisco (US)
- Department of Radiology and Nuclear Medicine VU University Medical Center Amsterdam the Netherlands
- Alzheimer center Amsterdam Amsterdam UMC, Amsterdam Neuroscience, VU University Amsterdam the Netherlands
- UCL Queen Square Institute of Neurology (GB)
- Alzheimer's Disease and Other Cognitive Disorders Unit, August Pi i Sunyer Biomedical Research Institute Barcelona Spain
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Erasmus MC (NL)
- Alzheimer Center, Department of Neurology Erasmus University Medical Center Rotterdam the Netherlands
- The University of Sydney (AU)
- Harvard University (US)
- Northwestern University (US)
- Hôpital de la Timone (FR)
- University of Toulouse, INSERM, Toulouse Neuroimaging Center Toulouse France
- University of British Columbia (CA)
- University of Pennsylvania (US)
- University of Manchester (GB)
- Center of Aging and Memory, Neurological Research Institute Buenos Aires Argentina
- Centre Hospitalier Universitaire de Besançon (FR)
- Department of Neurology, CHRU Besançon and Integrative and Clinical Neurosciences Laboratory, Regional Memory Center University of Bourgogne Franche‐Comté Besançon France
- Vita-Salute San Raffaele University (IT)
- Inserm (FR)
- Lund University (SE)
- Sunnybrook Health Science Centre (CA)
- Universidad Complutense de Madrid (ES)
- Department of Neurology and Nuclear Medicine, San Carlos Clinical Hospital, San Carlos Health Research Institute Complutense University of Madrid Madrid Spain
- Hôpital Fernand-Widal (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Université Paris-Sud (FR)
- Pitié-Salpêtrière Hospital (FR)
- The University of Melbourne (AU)
- Universitair Ziekenhuis Leuven (BE)
- University of California, Los Angeles (US)
- VA West Los Angeles Medical Center (US)
- University of Freiburg (DE)
- Universitat Autònoma de Barcelona (ES)
- Samsung Medical Center (KR)
- Technical University of Munich (DE)
- Department of Neurology Danish Dementia Research Center Copenhagen Denmark
- Marqués de Valdecilla University Hospital (ES)
- Maastricht University (NL)
- Université Laval (CA)
- Universitat Internacional de Catalunya (ES)
- Corresponding author
- Bergeron, David
- ORCID
- Bergeron, David
- Gorno‐Tempini, Maria L.
- Rabinovici, Gil D.
- Santos‐Santos, Miguel A.
- Seeley, William
- Miller, Bruce L.
- Pijnenburg, Yolande
- Groot, Colin
- Scheltens, Philip
- Rohrer, Jonathan D.
- Warren, Jason D.
- Schott, Jonathan M.
- Fox, Nick C.
- Grau‐Rivera, Oriol
- Seelaar, Harro
- Papma, Janne M.
- Hodges, John R.
- Leyton, Cristian E.
- Piguet, Olivier
- Rogalski, Emily J.
- Mesulam, Marsel M.
- Koric, Lejla
- Dickerson, Bradford
- Mackenzie, Ian R.
- Hsiung, Ging‐Yuek R.
- Belliard, Serge
- Irwin, David J.
- Wolk, David A.
- Grossman, Murray
- Jones, Matthew
- Mann, David
- Snowden, Julie S.
- Calandri, Ismael L.
- Miguet‐Alfonsi, Carole
- 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.
- 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
- Chételat, Gaël
- Jansen, Willemijn
- Laforce, Robert Jr.
- Visser, Pieter Jelle
- Ossenkoppele, Rik
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2018-11
- Volume
- 84
- Issue
- 5
- Pages
- 729-740
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC6354051
- OpenAlex
- W2894273961
- Cited by
- 203
- References
- 75
- Citations by year
- 2026: 20 · 2025: 29 · 2024: 25 · 2023: 24 · 2022: 33 · 2021: 32 · 2020: 28 · 2019: 12
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- HAL (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Lirias (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- primary progressive aphasia, amyloid-beta pathology, logopenic variant, semantic variant, APOE ε4, Alzheimer's disease, frontotemporal lobar degeneration, TDP-43, tau protein, amyloid PET, cerebrospinal fluid biomarkers, neuropathology, individual patient data
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Apolipoproteins E, Brain, Female, Genotype, Humans, Male, Middle Aged, Prevalence, Amyloid beta-Peptides, Aphasia, Primary Progressive
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