Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics

Tijms, Betty M.|||0000-0002-2612-1797; Gobom, Johan|||0000-0001-6193-6193; Reus, Lianne|||0000-0001-6936-242X; Jansen, Iris E.|||0000-0003-1901-8131; Hong, Shengjun; Dobricic, Valerija|||0000-0001-8559-1097; Kilpert, Fabian; ten Kate, Mara|||0000-0002-8290-8543; Barkhof, Frederik|||0000-0003-3543-3706; Tsolaki, Magda|||0000-0002-2072-8010; Verhey, Frans R. J.; Popp, Julius|||0000-0002-0068-0312; Martinez-Lage, Pablo|||0000-0001-5404-9967; Vandenberghe, Rik|||0000-0001-6237-2502; Lleó, Alberto|||0000-0002-2568-5478; Molinuevo, José Luis|||0000-0003-0485-6001; Engelborghs, Sebastiaan|||0000-0003-0304-9785; Bertram, Lars|||0000-0002-0108-124X; Lovestone, Simon|||0000-0003-0473-4565; Streffer, Johannes Rolf|||0000-0002-9387-5951; Vos, Stephanie J.B.|||0000-0002-2045-9818; Bos, Isabelle|||0000-0001-9648-6428; Blennow, Kaj|||0000-0002-1890-4193; Scheltens, Philip|||0000-0002-1046-6408; Teunissen, Charlotte E.|||0000-0002-4061-0837; Zetterberg, Henrik|||0000-0003-3930-4354; Visser, Pieter Jelle|||0000-0001-8008-9727

Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics

Using CSF proteomics, Tijms et al. identify three Alzheimer's disease subtypes that show: 1) hyperplasticity and increased BACE1 levels; 2) innate immune activation; and 3) blood-brain barrier dysfunction with low BACE1 levels. Future therapeutics may need tailoring to individual disease subtyp...

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Autores:	Tijms, Betty M.\|\|\|0000-0002-2612-1797, Gobom, Johan\|\|\|0000-0001-6193-6193, Reus, Lianne\|\|\|0000-0001-6936-242X, Jansen, Iris E.\|\|\|0000-0003-1901-8131, Hong, Shengjun, Dobricic, Valerija\|\|\|0000-0001-8559-1097, Kilpert, Fabian, ten Kate, Mara\|\|\|0000-0002-8290-8543, Barkhof, Frederik\|\|\|0000-0003-3543-3706, Tsolaki, Magda\|\|\|0000-0002-2072-8010, Verhey, Frans R. J., Popp, Julius\|\|\|0000-0002-0068-0312, Martinez-Lage, Pablo\|\|\|0000-0001-5404-9967, Vandenberghe, Rik\|\|\|0000-0001-6237-2502, Lleó, Alberto\|\|\|0000-0002-2568-5478, Molinuevo, José Luis\|\|\|0000-0003-0485-6001, Engelborghs, Sebastiaan\|\|\|0000-0003-0304-9785, Bertram, Lars\|\|\|0000-0002-0108-124X, Lovestone, Simon\|\|\|0000-0003-0473-4565, Streffer, Johannes Rolf\|\|\|0000-0002-9387-5951, Vos, Stephanie J.B.\|\|\|0000-0002-2045-9818, Bos, Isabelle\|\|\|0000-0001-9648-6428, Blennow, Kaj\|\|\|0000-0002-1890-4193, Scheltens, Philip\|\|\|0000-0002-1046-6408, Teunissen, Charlotte E.\|\|\|0000-0002-4061-0837, Zetterberg, Henrik\|\|\|0000-0003-3930-4354, Visser, Pieter Jelle\|\|\|0000-0001-8008-9727
Tipo de documento:	artigo
Data de publicação:	2020
País:	España
Recursos:	Universitat Autònoma de Barcelona
Repositório:	Dipòsit Digital de Documents de la UAB
Idioma:	inglês
OAI Identifier:	oai:ddd.uab.cat:235958
Acesso em linha:	https://ddd.uab.cat/record/235958 https://dx.doi.org/urn:doi:10.1093/brain/awaa325
Access Level:	Acceso aberto
Palavra-chave:	Alzheimer's disease Cerebrospinal fluid Proteomics Subtypes

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spelling	Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomicsTijms, Betty M.\|\|\|0000-0002-2612-1797Gobom, Johan\|\|\|0000-0001-6193-6193Reus, Lianne\|\|\|0000-0001-6936-242XJansen, Iris E.\|\|\|0000-0003-1901-8131Hong, ShengjunDobricic, Valerija\|\|\|0000-0001-8559-1097Kilpert, Fabianten Kate, Mara\|\|\|0000-0002-8290-8543Barkhof, Frederik\|\|\|0000-0003-3543-3706Tsolaki, Magda\|\|\|0000-0002-2072-8010Verhey, Frans R. J.Popp, Julius\|\|\|0000-0002-0068-0312Martinez-Lage, Pablo\|\|\|0000-0001-5404-9967Vandenberghe, Rik\|\|\|0000-0001-6237-2502Lleó, Alberto\|\|\|0000-0002-2568-5478Molinuevo, José Luis\|\|\|0000-0003-0485-6001Engelborghs, Sebastiaan\|\|\|0000-0003-0304-9785Bertram, Lars\|\|\|0000-0002-0108-124XLovestone, Simon\|\|\|0000-0003-0473-4565Streffer, Johannes Rolf\|\|\|0000-0002-9387-5951Vos, Stephanie J.B.\|\|\|0000-0002-2045-9818Bos, Isabelle\|\|\|0000-0001-9648-6428Blennow, Kaj\|\|\|0000-0002-1890-4193Scheltens, Philip\|\|\|0000-0002-1046-6408Teunissen, Charlotte E.\|\|\|0000-0002-4061-0837Zetterberg, Henrik\|\|\|0000-0003-3930-4354Visser, Pieter Jelle\|\|\|0000-0001-8008-9727Alzheimer's diseaseCerebrospinal fluidProteomicsSubtypesUsing CSF proteomics, Tijms et al. identify three Alzheimer's disease subtypes that show: 1) hyperplasticity and increased BACE1 levels; 2) innate immune activation; and 3) blood-brain barrier dysfunction with low BACE1 levels. Future therapeutics may need tailoring to individual disease subtypes. Alzheimer's disease is biologically heterogeneous, and detailed understanding of the processes involved in patients is critical for development of treatments. CSF contains hundreds of proteins, with concentrations reflecting ongoing (patho)physiological processes. This provides the opportunity to study many biological processes at the same time in patients. We studied whether Alzheimer's disease biological subtypes can be detected in CSF proteomics using the dual clustering technique non-negative matrix factorization. In two independent cohorts (EMIF-AD MBD and ADNI) we found that 705 (77% of 911 tested) proteins differed between Alzheimer's disease (defined as having abnormal amyloid, n = 425) and controls (defined as having normal CSF amyloid and tau and normal cognition, n = 127). Using these proteins for data-driven clustering, we identified three robust pathophysiological Alzheimer's disease subtypes within each cohort showing (i) hyperplasticity and increased BACE1 levels; (ii) innate immune activation; and (iii) blood-brain barrier dysfunction with low BACE1 levels. In both cohorts, the majority of individuals were labelled as having subtype 1 (80, 36% in EMIF-AD MBD; 117, 59% in ADNI), 71 (32%) in EMIF-AD MBD and 41 (21%) in ADNI were labelled as subtype 2, and 72 (32%) in EMIF-AD MBD and 39 (20%) individuals in ADNI were labelled as subtype 3. Genetic analyses showed that all subtypes had an excess of genetic risk for Alzheimer's disease (all P.Universitat Autònoma de Barcelona 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/235958https://dx.doi.org/urn:doi:10.1093/brain/awaa325reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2359582026-06-06T12:50:31Z
dc.title.none.fl_str_mv	Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics
title	Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics
spellingShingle	Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics Tijms, Betty M.\|\|\|0000-0002-2612-1797 Alzheimer's disease Cerebrospinal fluid Proteomics Subtypes
title_short	Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics
title_full	Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics
title_fullStr	Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics
title_full_unstemmed	Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics
title_sort	Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics
dc.creator.none.fl_str_mv	Tijms, Betty M.\|\|\|0000-0002-2612-1797 Gobom, Johan\|\|\|0000-0001-6193-6193 Reus, Lianne\|\|\|0000-0001-6936-242X Jansen, Iris E.\|\|\|0000-0003-1901-8131 Hong, Shengjun Dobricic, Valerija\|\|\|0000-0001-8559-1097 Kilpert, Fabian ten Kate, Mara\|\|\|0000-0002-8290-8543 Barkhof, Frederik\|\|\|0000-0003-3543-3706 Tsolaki, Magda\|\|\|0000-0002-2072-8010 Verhey, Frans R. J. Popp, Julius\|\|\|0000-0002-0068-0312 Martinez-Lage, Pablo\|\|\|0000-0001-5404-9967 Vandenberghe, Rik\|\|\|0000-0001-6237-2502 Lleó, Alberto\|\|\|0000-0002-2568-5478 Molinuevo, José Luis\|\|\|0000-0003-0485-6001 Engelborghs, Sebastiaan\|\|\|0000-0003-0304-9785 Bertram, Lars\|\|\|0000-0002-0108-124X Lovestone, Simon\|\|\|0000-0003-0473-4565 Streffer, Johannes Rolf\|\|\|0000-0002-9387-5951 Vos, Stephanie J.B.\|\|\|0000-0002-2045-9818 Bos, Isabelle\|\|\|0000-0001-9648-6428 Blennow, Kaj\|\|\|0000-0002-1890-4193 Scheltens, Philip\|\|\|0000-0002-1046-6408 Teunissen, Charlotte E.\|\|\|0000-0002-4061-0837 Zetterberg, Henrik\|\|\|0000-0003-3930-4354 Visser, Pieter Jelle\|\|\|0000-0001-8008-9727
author	Tijms, Betty M.\|\|\|0000-0002-2612-1797
author_facet	Tijms, Betty M.\|\|\|0000-0002-2612-1797 Gobom, Johan\|\|\|0000-0001-6193-6193 Reus, Lianne\|\|\|0000-0001-6936-242X Jansen, Iris E.\|\|\|0000-0003-1901-8131 Hong, Shengjun Dobricic, Valerija\|\|\|0000-0001-8559-1097 Kilpert, Fabian ten Kate, Mara\|\|\|0000-0002-8290-8543 Barkhof, Frederik\|\|\|0000-0003-3543-3706 Tsolaki, Magda\|\|\|0000-0002-2072-8010 Verhey, Frans R. J. Popp, Julius\|\|\|0000-0002-0068-0312 Martinez-Lage, Pablo\|\|\|0000-0001-5404-9967 Vandenberghe, Rik\|\|\|0000-0001-6237-2502 Lleó, Alberto\|\|\|0000-0002-2568-5478 Molinuevo, José Luis\|\|\|0000-0003-0485-6001 Engelborghs, Sebastiaan\|\|\|0000-0003-0304-9785 Bertram, Lars\|\|\|0000-0002-0108-124X Lovestone, Simon\|\|\|0000-0003-0473-4565 Streffer, Johannes Rolf\|\|\|0000-0002-9387-5951 Vos, Stephanie J.B.\|\|\|0000-0002-2045-9818 Bos, Isabelle\|\|\|0000-0001-9648-6428 Blennow, Kaj\|\|\|0000-0002-1890-4193 Scheltens, Philip\|\|\|0000-0002-1046-6408 Teunissen, Charlotte E.\|\|\|0000-0002-4061-0837 Zetterberg, Henrik\|\|\|0000-0003-3930-4354 Visser, Pieter Jelle\|\|\|0000-0001-8008-9727
author_role	author
author2	Gobom, Johan\|\|\|0000-0001-6193-6193 Reus, Lianne\|\|\|0000-0001-6936-242X Jansen, Iris E.\|\|\|0000-0003-1901-8131 Hong, Shengjun Dobricic, Valerija\|\|\|0000-0001-8559-1097 Kilpert, Fabian ten Kate, Mara\|\|\|0000-0002-8290-8543 Barkhof, Frederik\|\|\|0000-0003-3543-3706 Tsolaki, Magda\|\|\|0000-0002-2072-8010 Verhey, Frans R. J. Popp, Julius\|\|\|0000-0002-0068-0312 Martinez-Lage, Pablo\|\|\|0000-0001-5404-9967 Vandenberghe, Rik\|\|\|0000-0001-6237-2502 Lleó, Alberto\|\|\|0000-0002-2568-5478 Molinuevo, José Luis\|\|\|0000-0003-0485-6001 Engelborghs, Sebastiaan\|\|\|0000-0003-0304-9785 Bertram, Lars\|\|\|0000-0002-0108-124X Lovestone, Simon\|\|\|0000-0003-0473-4565 Streffer, Johannes Rolf\|\|\|0000-0002-9387-5951 Vos, Stephanie J.B.\|\|\|0000-0002-2045-9818 Bos, Isabelle\|\|\|0000-0001-9648-6428 Blennow, Kaj\|\|\|0000-0002-1890-4193 Scheltens, Philip\|\|\|0000-0002-1046-6408 Teunissen, Charlotte E.\|\|\|0000-0002-4061-0837 Zetterberg, Henrik\|\|\|0000-0003-3930-4354 Visser, Pieter Jelle\|\|\|0000-0001-8008-9727
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv	Alzheimer's disease Cerebrospinal fluid Proteomics Subtypes
topic	Alzheimer's disease Cerebrospinal fluid Proteomics Subtypes
description	Using CSF proteomics, Tijms et al. identify three Alzheimer's disease subtypes that show: 1) hyperplasticity and increased BACE1 levels; 2) innate immune activation; and 3) blood-brain barrier dysfunction with low BACE1 levels. Future therapeutics may need tailoring to individual disease subtypes. Alzheimer's disease is biologically heterogeneous, and detailed understanding of the processes involved in patients is critical for development of treatments. CSF contains hundreds of proteins, with concentrations reflecting ongoing (patho)physiological processes. This provides the opportunity to study many biological processes at the same time in patients. We studied whether Alzheimer's disease biological subtypes can be detected in CSF proteomics using the dual clustering technique non-negative matrix factorization. In two independent cohorts (EMIF-AD MBD and ADNI) we found that 705 (77% of 911 tested) proteins differed between Alzheimer's disease (defined as having abnormal amyloid, n = 425) and controls (defined as having normal CSF amyloid and tau and normal cognition, n = 127). Using these proteins for data-driven clustering, we identified three robust pathophysiological Alzheimer's disease subtypes within each cohort showing (i) hyperplasticity and increased BACE1 levels; (ii) innate immune activation; and (iii) blood-brain barrier dysfunction with low BACE1 levels. In both cohorts, the majority of individuals were labelled as having subtype 1 (80, 36% in EMIF-AD MBD; 117, 59% in ADNI), 71 (32%) in EMIF-AD MBD and 41 (21%) in ADNI were labelled as subtype 2, and 72 (32%) in EMIF-AD MBD and 39 (20%) individuals in ADNI were labelled as subtype 3. Genetic analyses showed that all subtypes had an excess of genetic risk for Alzheimer's disease (all P.
publishDate	2020
dc.date.none.fl_str_mv	2 2020-01-01 2020 2020-01-01
dc.type.none.fl_str_mv	Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://ddd.uab.cat/record/235958 https://dx.doi.org/urn:doi:10.1093/brain/awaa325
url	https://ddd.uab.cat/record/235958 https://dx.doi.org/urn:doi:10.1093/brain/awaa325
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.source.none.fl_str_mv	reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona
instname_str	Universitat Autònoma de Barcelona
reponame_str	Dipòsit Digital de Documents de la UAB
collection	Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics

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