Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer's disease progression
Introduction: We studied how biomarkers of reactive astrogliosis mediate the pathogenic cascade in the earliest Alzheimer's disease (AD) stages. Methods: We performed path analysis on data from 384 cognitively unimpaired individuals from the ALzheimer and FAmilies (ALFA)+ study using struct...
| Autores: | , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universitat Pompeu Fabra |
| Repositorio: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/59883 |
| Acceso en línea: | http://hdl.handle.net/10230/59883 http://dx.doi.org/10.1002/alz.13450 |
| Access Level: | acceso abierto |
| Palabra clave: | AD cascade Astrogliosis Biomarkers Chitinase-3-like protein 1 (YKL-40) Glial fibrillary acidic protein (GFAP) Preclinical Alzheimer&apos s disease Structural equation modeling |
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Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer's disease progression |
| title |
Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer's disease progression |
| spellingShingle |
Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer's disease progression Pelkmans, Wiesje AD cascade Astrogliosis Biomarkers Chitinase-3-like protein 1 (YKL-40) Glial fibrillary acidic protein (GFAP) Preclinical Alzheimer&apos s disease Structural equation modeling |
| title_short |
Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer's disease progression |
| title_full |
Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer's disease progression |
| title_fullStr |
Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer's disease progression |
| title_full_unstemmed |
Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer's disease progression |
| title_sort |
Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer's disease progression |
| dc.creator.none.fl_str_mv |
Pelkmans, Wiesje Shekari, Mahnaz Brugulat Serrat, Anna, 1986- Sánchez Benavides, Gonzalo Minguillón, Carolina Fauria, Karine Molinuevo, José Luis Grau, Oriol (Grau Rivera) González Escalante, Armand Kollmorgen, Gwendlyn Carboni, Margherita Ashton, Nicholas J. Zetterberg, Henrik Blennow, Kaj Suárez-Calvet, Marc Gispert, Juan Domingo ALFA Study |
| author |
Pelkmans, Wiesje |
| author_facet |
Pelkmans, Wiesje Shekari, Mahnaz Brugulat Serrat, Anna, 1986- Sánchez Benavides, Gonzalo Minguillón, Carolina Fauria, Karine Molinuevo, José Luis Grau, Oriol (Grau Rivera) González Escalante, Armand Kollmorgen, Gwendlyn Carboni, Margherita Ashton, Nicholas J. Zetterberg, Henrik Blennow, Kaj Suárez-Calvet, Marc Gispert, Juan Domingo ALFA Study |
| author_role |
author |
| author2 |
Shekari, Mahnaz Brugulat Serrat, Anna, 1986- Sánchez Benavides, Gonzalo Minguillón, Carolina Fauria, Karine Molinuevo, José Luis Grau, Oriol (Grau Rivera) González Escalante, Armand Kollmorgen, Gwendlyn Carboni, Margherita Ashton, Nicholas J. Zetterberg, Henrik Blennow, Kaj Suárez-Calvet, Marc Gispert, Juan Domingo ALFA Study |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
AD cascade Astrogliosis Biomarkers Chitinase-3-like protein 1 (YKL-40) Glial fibrillary acidic protein (GFAP) Preclinical Alzheimer&apos s disease Structural equation modeling |
| topic |
AD cascade Astrogliosis Biomarkers Chitinase-3-like protein 1 (YKL-40) Glial fibrillary acidic protein (GFAP) Preclinical Alzheimer&apos s disease Structural equation modeling |
| description |
Introduction: We studied how biomarkers of reactive astrogliosis mediate the pathogenic cascade in the earliest Alzheimer's disease (AD) stages. Methods: We performed path analysis on data from 384 cognitively unimpaired individuals from the ALzheimer and FAmilies (ALFA)+ study using structural equation modeling to quantify the relationships between biomarkers of reactive astrogliosis and the AD pathological cascade. Results: Cerebrospinal fluid (CSF) amyloid beta (Aβ)42/40 was associated with Aβ aggregation on positron emission tomography (PET) and with CSF p-tau181 , which was in turn directly associated with CSF neurofilament light (NfL). Plasma glial fibrillary acidic protein (GFAP) mediated the relationship between CSF Aβ42/40 and Aβ-PET, and CSF YKL-40 partly explained the association between Aβ-PET, p-tau181 , and NfL. Discussion: Our results suggest that reactive astrogliosis, as indicated by different fluid biomarkers, influences the pathogenic cascade during the preclinical stage of AD. While plasma GFAP mediates the early association between soluble and insoluble Aβ, CSF YKL-40 mediates the latter association between Aβ and downstream Aβ-induced tau pathology and tau-induced neuronal injury. Highlights: Lower CSF Aβ42/40 was directly linked to higher plasma GFAP concentrations. Plasma GFAP partially explained the relationship between soluble Aβ and insoluble Aβ. CSF YKL-40 mediated Aβ-induced tau phosphorylation and tau-induced neuronal injury. |
| 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 |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/59883 http://dx.doi.org/10.1002/alz.13450 |
| url |
http://hdl.handle.net/10230/59883 http://dx.doi.org/10.1002/alz.13450 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Alzheimers Dement. 2024 Jan;20(1):483-93 info:eu-repo/grantAgreement/EC/HE/101053962 info:eu-repo/grantAgreement/EC/H2020/948677 info:eu-repo/grantAgreement/EC/H2020/847648 info:eu-repo/grantAgreement/ES/2PE/RTI2018‑102261 info:eu-repo/grantAgreement/ES/2PE/PID2020-119556RA-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:Repositorio Digital de la UPF instname:Universitat Pompeu Fabra |
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Universitat Pompeu Fabra |
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Repositorio Digital de la UPF |
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Repositorio Digital de la UPF |
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1869420068320837632 |
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Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer's disease progressionPelkmans, WiesjeShekari, MahnazBrugulat Serrat, Anna, 1986-Sánchez Benavides, GonzaloMinguillón, CarolinaFauria, KarineMolinuevo, José LuisGrau, Oriol (Grau Rivera)González Escalante, ArmandKollmorgen, GwendlynCarboni, MargheritaAshton, Nicholas J.Zetterberg, HenrikBlennow, KajSuárez-Calvet, MarcGispert, Juan DomingoALFA StudyAD cascadeAstrogliosisBiomarkersChitinase-3-like protein 1 (YKL-40)Glial fibrillary acidic protein (GFAP)Preclinical Alzheimer&aposs diseaseStructural equation modelingIntroduction: We studied how biomarkers of reactive astrogliosis mediate the pathogenic cascade in the earliest Alzheimer's disease (AD) stages. Methods: We performed path analysis on data from 384 cognitively unimpaired individuals from the ALzheimer and FAmilies (ALFA)+ study using structural equation modeling to quantify the relationships between biomarkers of reactive astrogliosis and the AD pathological cascade. Results: Cerebrospinal fluid (CSF) amyloid beta (Aβ)42/40 was associated with Aβ aggregation on positron emission tomography (PET) and with CSF p-tau181 , which was in turn directly associated with CSF neurofilament light (NfL). Plasma glial fibrillary acidic protein (GFAP) mediated the relationship between CSF Aβ42/40 and Aβ-PET, and CSF YKL-40 partly explained the association between Aβ-PET, p-tau181 , and NfL. Discussion: Our results suggest that reactive astrogliosis, as indicated by different fluid biomarkers, influences the pathogenic cascade during the preclinical stage of AD. While plasma GFAP mediates the early association between soluble and insoluble Aβ, CSF YKL-40 mediates the latter association between Aβ and downstream Aβ-induced tau pathology and tau-induced neuronal injury. Highlights: Lower CSF Aβ42/40 was directly linked to higher plasma GFAP concentrations. Plasma GFAP partially explained the relationship between soluble Aβ and insoluble Aβ. CSF YKL-40 mediated Aβ-induced tau phosphorylation and tau-induced neuronal injury.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 (TriBEKa‑17‑519007). Additional support has been received from the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan government under grant no. 2017-SGR-892. 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 program under grant agreement 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 program under the Marie Skłodowska-Curie grant agreement 860197 (MIRIADE), the European Union Joint Programme – Neurodegenerative Disease Research (JPND2021-00694), and the UK Dementia Research Institute at UCL (UKDRI-1003). KB is supported by the Swedish Research Council (2017‑00915); the Alzheimer Drug Discovery Foundation (ADDF), USA (RDAPB‑201809‑2016615); the Swedish Alzheimer Foundation (AF‑742881); Hjärnfonden, Sweden (FO2017‑0243); the Swedish state under the agreement between the Swedish government and the county councils, the ALF‑agreement (ALFGBG‑715986); the European Union Joint Programme for Neurodegenerative Disorders (JPND2019‑466‑236); the National Institute of Health (NIH), USA (grant 1R01AG068398‑01); and the Alzheimer's Association 2021 Zenith Award (ZEN‑21‑848495). MSC receives funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement 948677), the Instituto de Salud Carlos III (PI19/00155, PI22/00456), and the ERC under the EU's ‘la Caixa’ Foundation (ID 100010434) and from the EU's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant (847648, LCF/BQ/PR21/11840004). JDG is supported by the Spanish Ministry of Science and Innovation (RYC‑2013‑13054). JDG has also received research support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking AMYPAD (grant agreement 115952), EIT Digital (grant 2021), and from Ministerio de Ciencia y Universidades (grant agreement RTI2018‑102261). GS-B receives funding from the Ministerio de Ciencia e Innovacion, Spanish Research Agency, PID2020-119556RA-I00. OGR receives funding from the Alzheimer's Association Research Fellowship Program (2019-AARF-644568), from Instituto de Salud Carlos III (PI19/00117), and from the Spanish Ministry of Science, Innovation and Universities (Juan de la Cierva programme IJC2020-043417-I).Wiley202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/59883http://dx.doi.org/10.1002/alz.13450reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésAlzheimers Dement. 2024 Jan;20(1):483-93info:eu-repo/grantAgreement/EC/HE/101053962info:eu-repo/grantAgreement/EC/H2020/948677info:eu-repo/grantAgreement/EC/H2020/847648info:eu-repo/grantAgreement/ES/2PE/RTI2018‑102261info:eu-repo/grantAgreement/ES/2PE/PID2020-119556RA-I00© 2023 The Authors. 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:repositori.upf.edu:10230/598832026-06-12T07:21:37Z |
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15.812429 |