CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease
Introduction: We examined whether baseline glial markers soluble triggering receptor expressed on myeloid cell 2 (sTREM2), chitinase 3-like protein 1 (YKL-40), and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF), and plasma GFAP are associated with cognitive change in cognitively...
| Autores: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/61197 |
| Acceso en línea: | http://hdl.handle.net/10230/61197 http://dx.doi.org/10.1002/alz.13862 |
| Access Level: | acceso abierto |
| Palabra clave: | Alzheimer&apos s disease Chitinase 3‐like protein 1 Cognition Cognitively unimpaired Glial biomarkers Glial fibrillary acidic protein Preclinical Soluble triggering receptor expressed on myeloid cell 2 |
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CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease |
| title |
CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease |
| spellingShingle |
CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease Warmenhoven, Noëlle Alzheimer&apos s disease Chitinase 3‐like protein 1 Cognition Cognitively unimpaired Glial biomarkers Glial fibrillary acidic protein Preclinical Soluble triggering receptor expressed on myeloid cell 2 |
| title_short |
CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease |
| title_full |
CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease |
| title_fullStr |
CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease |
| title_full_unstemmed |
CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease |
| title_sort |
CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease |
| dc.creator.none.fl_str_mv |
Warmenhoven, Noëlle Sánchez Benavides, Gonzalo González Escalante, Armand Milà Alomà, Marta Shekari, Mahnaz López Martos, David Ortiz Romero, Paula, 1994- Kollmorgen, Gwendlyn Quijano Rubio, Clara Minguillón, Carolina Gispert, Juan Domingo Vilor Tejedor, Natàlia, 1988- Arenaza Urquijo, Eider M. Palpatzis, Eleni Ashton, Nicholas J. Zetterberg, Henrik Blennow, Kaj Suárez-Calvet, Marc Grau, Oriol (Grau Rivera) ALFA Study |
| author |
Warmenhoven, Noëlle |
| author_facet |
Warmenhoven, Noëlle Sánchez Benavides, Gonzalo González Escalante, Armand Milà Alomà, Marta Shekari, Mahnaz López Martos, David Ortiz Romero, Paula, 1994- Kollmorgen, Gwendlyn Quijano Rubio, Clara Minguillón, Carolina Gispert, Juan Domingo Vilor Tejedor, Natàlia, 1988- Arenaza Urquijo, Eider M. Palpatzis, Eleni Ashton, Nicholas J. Zetterberg, Henrik Blennow, Kaj Suárez-Calvet, Marc Grau, Oriol (Grau Rivera) ALFA Study |
| author_role |
author |
| author2 |
Sánchez Benavides, Gonzalo González Escalante, Armand Milà Alomà, Marta Shekari, Mahnaz López Martos, David Ortiz Romero, Paula, 1994- Kollmorgen, Gwendlyn Quijano Rubio, Clara Minguillón, Carolina Gispert, Juan Domingo Vilor Tejedor, Natàlia, 1988- Arenaza Urquijo, Eider M. Palpatzis, Eleni Ashton, Nicholas J. Zetterberg, Henrik Blennow, Kaj Suárez-Calvet, Marc Grau, Oriol (Grau Rivera) ALFA Study |
| author2_role |
author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Alzheimer&apos s disease Chitinase 3‐like protein 1 Cognition Cognitively unimpaired Glial biomarkers Glial fibrillary acidic protein Preclinical Soluble triggering receptor expressed on myeloid cell 2 |
| topic |
Alzheimer&apos s disease Chitinase 3‐like protein 1 Cognition Cognitively unimpaired Glial biomarkers Glial fibrillary acidic protein Preclinical Soluble triggering receptor expressed on myeloid cell 2 |
| description |
Introduction: We examined whether baseline glial markers soluble triggering receptor expressed on myeloid cell 2 (sTREM2), chitinase 3-like protein 1 (YKL-40), and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF), and plasma GFAP are associated with cognitive change in cognitively unimpaired (CU) individuals at risk of Alzheimer's disease (AD). Methods: A total of 353 CU (mean age 60.9 years) participants were included (mean follow-up time 3.28 years). Linear regression models with cognition as outcome were used. We also tested whether amyloid beta (Aβ) status modified these associations. Results: Higher baseline CSF sTREM2 was associated with a positive global cognition (Preclinical Alzheimer's Cognitive Composite) rate of change, and better memory and executive outcomes, independently of AD pathology. Higher baseline plasma GFAP was associated with a decline on attention rate of change. Stratified analyses by Aβ status showed that CSF sTREM2 and YKL-40 were positively associated with executive functioning in amyloid negative (Aβ-) individuals. Discussion: Our results suggest that a TREM2-mediated microglial response may be associated with better longitudinal cognitive performance. Highlights: Higher cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cell 2 (sTREM2) relates to better longitudinal cognitive performance. The association between CSF sTREM2 and cognition is independent of Alzheimer's disease (AD) pathology. Targeting microglial reactivity may be a therapeutic strategy for AD prevention. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024 2024 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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http://hdl.handle.net/10230/61197 http://dx.doi.org/10.1002/alz.13862 |
| url |
http://hdl.handle.net/10230/61197 http://dx.doi.org/10.1002/alz.13862 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Alzheimers Dement. 2024 Sep;20(9):5819-32 info:eu-repo/grantAgreement/EC/HE/101053962 info:eu-repo/grantAgreement/ES/2PE/PID2020-119556RA-I00 info:eu-repo/grantAgreement/ES/2PE/PID2019-111514RA-I00 info:eu-repo/grantAgreement/EC/H2020/860197 info:eu-repo/grantAgreement/EC/H2020/948677 info:eu-repo/grantAgreement/EC/H2020/847648 info:eu-repo/grantAgreement/ES/3PE/PID2022-143106OA-I00 |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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application/pdf application/pdf |
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Wiley |
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Wiley |
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reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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1869411085767933952 |
| spelling |
CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's diseaseWarmenhoven, NoëlleSánchez Benavides, GonzaloGonzález Escalante, ArmandMilà Alomà, MartaShekari, MahnazLópez Martos, DavidOrtiz Romero, Paula, 1994-Kollmorgen, GwendlynQuijano Rubio, ClaraMinguillón, CarolinaGispert, Juan DomingoVilor Tejedor, Natàlia, 1988-Arenaza Urquijo, Eider M.Palpatzis, EleniAshton, Nicholas J.Zetterberg, HenrikBlennow, KajSuárez-Calvet, MarcGrau, Oriol (Grau Rivera)ALFA StudyAlzheimer&aposs diseaseChitinase 3‐like protein 1CognitionCognitively unimpairedGlial biomarkersGlial fibrillary acidic proteinPreclinicalSoluble triggering receptor expressed on myeloid cell 2Introduction: We examined whether baseline glial markers soluble triggering receptor expressed on myeloid cell 2 (sTREM2), chitinase 3-like protein 1 (YKL-40), and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF), and plasma GFAP are associated with cognitive change in cognitively unimpaired (CU) individuals at risk of Alzheimer's disease (AD). Methods: A total of 353 CU (mean age 60.9 years) participants were included (mean follow-up time 3.28 years). Linear regression models with cognition as outcome were used. We also tested whether amyloid beta (Aβ) status modified these associations. Results: Higher baseline CSF sTREM2 was associated with a positive global cognition (Preclinical Alzheimer's Cognitive Composite) rate of change, and better memory and executive outcomes, independently of AD pathology. Higher baseline plasma GFAP was associated with a decline on attention rate of change. Stratified analyses by Aβ status showed that CSF sTREM2 and YKL-40 were positively associated with executive functioning in amyloid negative (Aβ-) individuals. Discussion: Our results suggest that a TREM2-mediated microglial response may be associated with better longitudinal cognitive performance. Highlights: Higher cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cell 2 (sTREM2) relates to better longitudinal cognitive performance. The association between CSF sTREM2 and cognition is independent of Alzheimer's disease (AD) pathology. Targeting microglial reactivity may be a therapeutic strategy for AD prevention.This publication is part of the ALFA study (ALzheimers and Families). The authors would like to thank the collaborators of the ALFA study. Additionally, the authors would like to express their most sincere gratitude to the ALFA project participants and relatives without whom this research would not have been possible. The authors thank Roche Diagnostics International Ltd for providing the kits to measure CSF biomarkers and GE Healthcare for providing the doses of [18F]flutemetamol PET. The Roche NeuroToolKit is a panel of exploratory prototype assays designed to robustly evaluate biomarkers associated with key pathologic events characteristic of AD and other neurological disorders, used for research purposes only and not approved for clinical use. COBAS and ELECSYS are trademarks of Roche. All other product names and trademarks are the property of their respective owners. The ALFA+ study receives funding from “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/GN17/50300004 and the Alzheimer's Association and an international anonymous charity foundation through the TriBEKa Imaging Platform project (TriBEKa17519007). Additional support has been received from the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under the grant no. 2021 SGR 00913. GSB is supported by the Spanish Ministry of Science and Innovation - State Research Agency MCIN/AEI/10.13039/501100011033 through the project PID2020-119556RA-I00 and by the Instituto de Salud Carlos III (ISCIII) through the project CP23/00039 (Miguel Servet Contract), so-funded by the European Union (FSE+). DLM is supported by the Instituto de Salud Carlos III (ISCIII) through the project PI19/00117 (co-funded by European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future”). CM received funding within the context of EURO-FINGERS, a EU Joint Programme – Neurodegenerative Disease Research (JPND) project. The EURO-FINGERS project is supported through the following funding organizations under the aegis of JPND—www.jpnd.eu: Finland: Academy of Finland; Germany: Federal Ministry of Education and Research; Spain: National Institute of Health Carlos III; Luxembourg: National Research Fund; Hungary: National Research, Development and Innovation Office; and The Netherlands: Netherlands Organisation for Health Research and Development (ZonMW-Memorabel no. 733051102). JDG has received research support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking AMYPAD (grant agreement 115952), Innovative Health Initiative PROMINENT (grant agreement 101112145), EIT Digital (Grant 2021), and from the Spanish Ministry of Science and Innovation - State Research Agency MCIN/AEI/10.13039/501100011033 through the project RTI2018102261. EAU has received funding by the Ministry of Science and Innovation (PID2019-111514RA-I00), the Alzheimer's Association research grants (AARG 2019-AARG-644641, AARG 2019-AARG-644641-RAPID), and the European Union Joint Program for Neurodegenerative Disorders (JPND2022-138, AC22/00060). EAU is also supported by the Spanish Ministry of Science and Innovation—State Research Agency (RYC2018-026053-I), co-funded by the European Social Fund (ESF). EP is funded by the Spanish Ministry of Science and Innovation (PRE2020-095827). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2022-01018 and #2019-02397), the European Union's Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C, and #ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme – Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003). KB is supported by the Swedish Research Council (#201700915); the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB2018092016615); the Swedish Alzheimer Foundation (#AF742881); Hjärnfonden, Sweden (#FO20170243); the Swedish state under the agreement between the Swedish government and the County Councils, the ALFagreement (#ALFGBG715986); the European Union Joint Program for Neurodegenerative Disorders (JPND2019466236); the National Institute of Health (NIH), USA (grant #1R01AG06839801); and the Alzheimer's Association 2021 Zenith Award (ZEN21848495). MSC receives funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant agreement No. 948677), the Instituto de Salud Carlos III (ISCIII) through the projects PI19/00155 and PI22/00456 (Co-funded by European Regional Development Fund (FEDER) “A way to make Europe”), and receives the support of a fellowship funded by “la Caixa” Foundation (ID 100010434), and the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 847648 (fellowship code LCF/BQ/PR21/11840004). OGR receives funding from the Alzheimer's Association Research Fellowship Program (2019-AARF-644568), from Instituto de Salud Carlos III (ISCIII) through the project PI19/00117 co-funded by the European Union (FEDER), and from Spanish Ministry of Science and Innovation - State Research Agency MCIN/AEI/10.13039/501100011033 through the project IJC2020-043417-I, co-funded by the European Union “Next GenerationEU”/PRTR. NVT is supported by the Spanish Ministry of Science and Innovation - State Research Agency MCIN/AEI/10.13039/501100011033 through the project IJDC2020-043216-I, co-funded by the European Union “Next GenerationEU”/PRTR) and project PID2022-143106OA-I00, co-funded by the European Union (FEDER). In addition, NVT receives funding from the Alzheimer's Disease Data Initiative (ADDI) through the Williams H. Gates Sr. Fellowship Program and the Ajuntament de Barcelona in collaboration with “la Caixa” Foundation though the project 23S06083-001.Wiley202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/61197http://dx.doi.org/10.1002/alz.13862reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésAlzheimers Dement. 2024 Sep;20(9):5819-32info:eu-repo/grantAgreement/EC/HE/101053962info:eu-repo/grantAgreement/ES/2PE/PID2020-119556RA-I00info:eu-repo/grantAgreement/ES/2PE/PID2019-111514RA-I00info:eu-repo/grantAgreement/EC/H2020/860197info:eu-repo/grantAgreement/EC/H2020/948677info:eu-repo/grantAgreement/EC/H2020/847648info:eu-repo/grantAgreement/ES/3PE/PID2022-143106OA-I00© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/611972026-05-29T05:05:01Z |
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15,198674 |