Linking genomic and proteomic signatures to brain amyloid burden
Alzheimer's disease (AD) is a complex disease with a strong genetic component, yet many genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:dnet:uabarcelona_::07a49065356be0ef3fefe1390aeaa07f |
| Acceso en línea: | https://ddd.uab.cat/record/328493 https://dx.doi.org/urn:doi:10.1007/s10142-025-01581-6 |
| Access Level: | acceso abierto |
| Palabra clave: | Aβ42 CSF biomarkers PET tomography GWAS Proteome |
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| dc.title.none.fl_str_mv |
Linking genomic and proteomic signatures to brain amyloid burden insights from GR@ACE/DEGESCO |
| title |
Linking genomic and proteomic signatures to brain amyloid burden |
| spellingShingle |
Linking genomic and proteomic signatures to brain amyloid burden Puerta, Raquel|||0000-0002-1191-5893 Aβ42 CSF biomarkers PET tomography GWAS Proteome |
| title_short |
Linking genomic and proteomic signatures to brain amyloid burden |
| title_full |
Linking genomic and proteomic signatures to brain amyloid burden |
| title_fullStr |
Linking genomic and proteomic signatures to brain amyloid burden |
| title_full_unstemmed |
Linking genomic and proteomic signatures to brain amyloid burden |
| title_sort |
Linking genomic and proteomic signatures to brain amyloid burden |
| dc.creator.none.fl_str_mv |
Puerta, Raquel|||0000-0002-1191-5893 De Rojas, Itziar|||0000-0002-2148-381X García-González, Pablo|||0000-0003-0125-5403 Olivé Roig, Clàudia|||0000-0002-9438-5639 Sotolongo Grau, Oscar|||0000-0002-9679-0670 García-Sánchez, Ainhoa García-Gutiérrez, Fernando Montrreal Navarro, Laura|||0000-0002-0010-645X Tartari, Juan Pablo Sanabria, Ángela|||0000-0002-7501-9895 Pytel, Vanesa Lage, Carmen|||0000-0003-1703-121X Quintela, Inés|||0000-0002-0239-7975 Aguilera, Nuria Rodríguez-Rodríguez, Eloy|||0000-0001-7742-677X Alarcón-Martín, Emilio|||0000-0002-0985-872X Orellana del Río, Adelina|||0000-0002-0204-1944 Pastor, Pau|||0000-0002-7493-8777 Pérez-Tur, Jordi|||0000-0002-9111-1712 Piñol-Ripoll, Gerard Lopez de Munain, Adolfo|||0000-0002-9509-4032 García-Alberca, Jose María|||0000-0003-2951-6644 Royo, Jose Luís Bullido, María J.|||0000-0002-6477-1117 Alvarez, Victoria|||0000-0002-1916-2523 Real, Luis M.|||0000-0003-4932-7429 Gómez-Garre, Dulcenombre|||0000-0002-5056-6489 Franco-Macías, Emilio|||0000-0003-4186-1037 Mir, Pablo|||0000-0003-1656-302X Medina, Miguel|||0000-0002-7016-5340 Sanchez-Valle, Raquel|||0000-0001-7750-896X Dols Icardo, Oriol|||0000-0003-2656-8748 Sáez, María Eugenia|||0000-0001-9299-2534 Carracedo, Ángel|||0000-0003-1085-8986 Tárraga, Lluís|||0000-0002-8423-946X Valero, Sergi|||0000-0002-6599-948X Marquié, Marta|||0000-0002-0660-0950 Boada, Mercè|||0000-0003-2617-3009 Cano, Amanda|||0000-0001-9567-4283 Ruiz Laza, Agustín|||0000-0003-2633-2495 Corbatón-Anchuelo, Arturo Martínez-Larrad, María Teresa Alegret, Montse Sánchez-Juan, Pascual|||0000-0002-6081-8037 Cavazos, Jose Enrique Cabrera-Socorro, Alfredo |
| author |
Puerta, Raquel|||0000-0002-1191-5893 |
| author_facet |
Puerta, Raquel|||0000-0002-1191-5893 De Rojas, Itziar|||0000-0002-2148-381X García-González, Pablo|||0000-0003-0125-5403 Olivé Roig, Clàudia|||0000-0002-9438-5639 Sotolongo Grau, Oscar|||0000-0002-9679-0670 García-Sánchez, Ainhoa García-Gutiérrez, Fernando Montrreal Navarro, Laura|||0000-0002-0010-645X Tartari, Juan Pablo Sanabria, Ángela|||0000-0002-7501-9895 Pytel, Vanesa Lage, Carmen|||0000-0003-1703-121X Quintela, Inés|||0000-0002-0239-7975 Aguilera, Nuria Rodríguez-Rodríguez, Eloy|||0000-0001-7742-677X Alarcón-Martín, Emilio|||0000-0002-0985-872X Orellana del Río, Adelina|||0000-0002-0204-1944 Pastor, Pau|||0000-0002-7493-8777 Pérez-Tur, Jordi|||0000-0002-9111-1712 Piñol-Ripoll, Gerard Lopez de Munain, Adolfo|||0000-0002-9509-4032 García-Alberca, Jose María|||0000-0003-2951-6644 Royo, Jose Luís Bullido, María J.|||0000-0002-6477-1117 Alvarez, Victoria|||0000-0002-1916-2523 Real, Luis M.|||0000-0003-4932-7429 Gómez-Garre, Dulcenombre|||0000-0002-5056-6489 Franco-Macías, Emilio|||0000-0003-4186-1037 Mir, Pablo|||0000-0003-1656-302X Medina, Miguel|||0000-0002-7016-5340 Sanchez-Valle, Raquel|||0000-0001-7750-896X Dols Icardo, Oriol|||0000-0003-2656-8748 Sáez, María Eugenia|||0000-0001-9299-2534 Carracedo, Ángel|||0000-0003-1085-8986 Tárraga, Lluís|||0000-0002-8423-946X Valero, Sergi|||0000-0002-6599-948X Marquié, Marta|||0000-0002-0660-0950 Boada, Mercè|||0000-0003-2617-3009 Cano, Amanda|||0000-0001-9567-4283 Ruiz Laza, Agustín|||0000-0003-2633-2495 Corbatón-Anchuelo, Arturo Martínez-Larrad, María Teresa Alegret, Montse Sánchez-Juan, Pascual|||0000-0002-6081-8037 Cavazos, Jose Enrique Cabrera-Socorro, Alfredo |
| author_role |
author |
| author2 |
De Rojas, Itziar|||0000-0002-2148-381X García-González, Pablo|||0000-0003-0125-5403 Olivé Roig, Clàudia|||0000-0002-9438-5639 Sotolongo Grau, Oscar|||0000-0002-9679-0670 García-Sánchez, Ainhoa García-Gutiérrez, Fernando Montrreal Navarro, Laura|||0000-0002-0010-645X Tartari, Juan Pablo Sanabria, Ángela|||0000-0002-7501-9895 Pytel, Vanesa Lage, Carmen|||0000-0003-1703-121X Quintela, Inés|||0000-0002-0239-7975 Aguilera, Nuria Rodríguez-Rodríguez, Eloy|||0000-0001-7742-677X Alarcón-Martín, Emilio|||0000-0002-0985-872X Orellana del Río, Adelina|||0000-0002-0204-1944 Pastor, Pau|||0000-0002-7493-8777 Pérez-Tur, Jordi|||0000-0002-9111-1712 Piñol-Ripoll, Gerard Lopez de Munain, Adolfo|||0000-0002-9509-4032 García-Alberca, Jose María|||0000-0003-2951-6644 Royo, Jose Luís Bullido, María J.|||0000-0002-6477-1117 Alvarez, Victoria|||0000-0002-1916-2523 Real, Luis M.|||0000-0003-4932-7429 Gómez-Garre, Dulcenombre|||0000-0002-5056-6489 Franco-Macías, Emilio|||0000-0003-4186-1037 Mir, Pablo|||0000-0003-1656-302X Medina, Miguel|||0000-0002-7016-5340 Sanchez-Valle, Raquel|||0000-0001-7750-896X Dols Icardo, Oriol|||0000-0003-2656-8748 Sáez, María Eugenia|||0000-0001-9299-2534 Carracedo, Ángel|||0000-0003-1085-8986 Tárraga, Lluís|||0000-0002-8423-946X Valero, Sergi|||0000-0002-6599-948X Marquié, Marta|||0000-0002-0660-0950 Boada, Mercè|||0000-0003-2617-3009 Cano, Amanda|||0000-0001-9567-4283 Ruiz Laza, Agustín|||0000-0003-2633-2495 Corbatón-Anchuelo, Arturo Martínez-Larrad, María Teresa Alegret, Montse Sánchez-Juan, Pascual|||0000-0002-6081-8037 Cavazos, Jose Enrique Cabrera-Socorro, Alfredo |
| 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 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. Departament de Medicina |
| dc.subject.none.fl_str_mv |
Aβ42 CSF biomarkers PET tomography GWAS Proteome |
| topic |
Aβ42 CSF biomarkers PET tomography GWAS Proteome |
| description |
Alzheimer's disease (AD) is a complex disease with a strong genetic component, yet many genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of amyloid pathology, which may provide insights into the underlying biology of the disease. We performed a meta-GWAS of CSF Aβ42 and PET measures combining six independent cohorts (n = 2,076). Given the opposite beta direction of Aβ phenotypes in CSF and PET measures, only genetic signals showing opposite directions were considered for analysis (n = 376,599). We explored the amyloidosis signature in the CSF proteome using SOMAscan proteomics (ACE cohort, n = 1,008), connected it with GWAS loci modulating amyloidosis and performed an enrichment analysis of overlapping hits. Finally, we compared our results with a large meta-analysis using publicly available datasets in CSF (n = 13,409) and PET (n = 13,116). After filtering the meta-GWAS, we observed genome-wide significance in the rs429358-APOE locus and annotated nine suggestive hits. We replicated the APOE loci using the large CSF-PET meta-GWAS, identifying multiple AD-associated genes including the novel GADL1 locus. Additionally, we found 1,387 FDR-significant SOMAscan proteins associated with CSF Aβ42 levels. The overlap among GWAS loci and proteins associated with amyloid burden was minimal (n = 35). The enrichment analysis revealed mechanisms connecting amyloidosis with the plasma membrane's anchored component, synapse physiology and mental disorders that were replicated in the large CSF-PET meta-analysis. Combining CSF and PET amyloid GWAS with CSF proteome analyses may effectively elucidate causative molecular mechanisms behind amyloid mobilization and AD physiopathology. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2 2025-01-01 2025 2025-01-01 |
| 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/328493 https://dx.doi.org/urn:doi:10.1007/s10142-025-01581-6 |
| url |
https://ddd.uab.cat/record/328493 https://dx.doi.org/urn:doi:10.1007/s10142-025-01581-6 |
| 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-nd/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-nd/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 |
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Dipòsit Digital de Documents de la UAB |
| repository.name.fl_str_mv |
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| _version_ |
1869419772659105792 |
| spelling |
Linking genomic and proteomic signatures to brain amyloid burdeninsights from GR@ACE/DEGESCOPuerta, Raquel|||0000-0002-1191-5893De Rojas, Itziar|||0000-0002-2148-381XGarcía-González, Pablo|||0000-0003-0125-5403Olivé Roig, Clàudia|||0000-0002-9438-5639Sotolongo Grau, Oscar|||0000-0002-9679-0670García-Sánchez, AinhoaGarcía-Gutiérrez, FernandoMontrreal Navarro, Laura|||0000-0002-0010-645XTartari, Juan PabloSanabria, Ángela|||0000-0002-7501-9895Pytel, VanesaLage, Carmen|||0000-0003-1703-121XQuintela, Inés|||0000-0002-0239-7975Aguilera, NuriaRodríguez-Rodríguez, Eloy|||0000-0001-7742-677XAlarcón-Martín, Emilio|||0000-0002-0985-872XOrellana del Río, Adelina|||0000-0002-0204-1944Pastor, Pau|||0000-0002-7493-8777Pérez-Tur, Jordi|||0000-0002-9111-1712Piñol-Ripoll, GerardLopez de Munain, Adolfo|||0000-0002-9509-4032García-Alberca, Jose María|||0000-0003-2951-6644Royo, Jose LuísBullido, María J.|||0000-0002-6477-1117Alvarez, Victoria|||0000-0002-1916-2523Real, Luis M.|||0000-0003-4932-7429Gómez-Garre, Dulcenombre|||0000-0002-5056-6489Franco-Macías, Emilio|||0000-0003-4186-1037Mir, Pablo|||0000-0003-1656-302XMedina, Miguel|||0000-0002-7016-5340Sanchez-Valle, Raquel|||0000-0001-7750-896XDols Icardo, Oriol|||0000-0003-2656-8748Sáez, María Eugenia|||0000-0001-9299-2534Carracedo, Ángel|||0000-0003-1085-8986Tárraga, Lluís|||0000-0002-8423-946XValero, Sergi|||0000-0002-6599-948XMarquié, Marta|||0000-0002-0660-0950Boada, Mercè|||0000-0003-2617-3009Cano, Amanda|||0000-0001-9567-4283Ruiz Laza, Agustín|||0000-0003-2633-2495Corbatón-Anchuelo, ArturoMartínez-Larrad, María TeresaAlegret, MontseSánchez-Juan, Pascual|||0000-0002-6081-8037Cavazos, Jose EnriqueCabrera-Socorro, AlfredoAβ42CSF biomarkersPET tomographyGWASProteomeAlzheimer's disease (AD) is a complex disease with a strong genetic component, yet many genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of amyloid pathology, which may provide insights into the underlying biology of the disease. We performed a meta-GWAS of CSF Aβ42 and PET measures combining six independent cohorts (n = 2,076). Given the opposite beta direction of Aβ phenotypes in CSF and PET measures, only genetic signals showing opposite directions were considered for analysis (n = 376,599). We explored the amyloidosis signature in the CSF proteome using SOMAscan proteomics (ACE cohort, n = 1,008), connected it with GWAS loci modulating amyloidosis and performed an enrichment analysis of overlapping hits. Finally, we compared our results with a large meta-analysis using publicly available datasets in CSF (n = 13,409) and PET (n = 13,116). After filtering the meta-GWAS, we observed genome-wide significance in the rs429358-APOE locus and annotated nine suggestive hits. We replicated the APOE loci using the large CSF-PET meta-GWAS, identifying multiple AD-associated genes including the novel GADL1 locus. Additionally, we found 1,387 FDR-significant SOMAscan proteins associated with CSF Aβ42 levels. The overlap among GWAS loci and proteins associated with amyloid burden was minimal (n = 35). The enrichment analysis revealed mechanisms connecting amyloidosis with the plasma membrane's anchored component, synapse physiology and mental disorders that were replicated in the large CSF-PET meta-analysis. Combining CSF and PET amyloid GWAS with CSF proteome analyses may effectively elucidate causative molecular mechanisms behind amyloid mobilization and AD physiopathology.Universitat Autònoma de Barcelona. Departament de Medicina 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/328493https://dx.doi.org/urn:doi:10.1007/s10142-025-01581-6reponame: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, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:dnet:uabarcelona_::07a49065356be0ef3fefe1390aeaa07f2026-06-06T12:50:31Z |
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15.81155 |