Whole-brain modeling of the differential influences of amyloid-beta and tau in Alzheimer's disease

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• dc.contributor.author Patow, Gustavo
• dc.contributor.author Stefanovski, Leon
• dc.contributor.author Ritter, Petra
• dc.contributor.author Deco, Gustavo
• dc.contributor.author Kobeleva, Xenia
• dc.date.accessioned 2025-03-27T08:15:20Z
• dc.date.available 2025-03-27T08:15:20Z
• dc.date.issued 2023
• dc.description Includes supplementary materials for the online appendix.
• dc.description.abstract Background. Alzheimer’s disease is a neurodegenerative condition associated with the accumulation of two misfolded proteins, amyloid-beta (A) and tau. We study their effect on neuronal activity, with the aim of assessing their individual and combined impact. Methods. We use a whole-brain dynamic model to find the optimal parameters that best describe the effects of A and tau on the excitation-inhibition balance of the local nodes. Results. We found a clear dominance of A over tau in the early disease stages (MCI), while tau dominates over A in the latest stages (AD). We identify crucial roles for A and tau in complex neuronal dynamics and demonstrate the viability of using regional distributions to define models of large-scale brain function in AD. Conclusions. Our study provides further insight into the dynamics and complex interplay between these two proteins, opening the path for further investigations on biomarkers and candidate therapeutic targets in-silico.
• dc.description.sponsorship This research was funded by Grant PID2021-122136OB-C22 funded by MCIN/AEI/ 10.13039/501100011033 and by ERDF A way of making Europe of GP. This work was supported by an add-on fellowship of the Joachim Herz Foundation of XK. G.D. was supported by the project NEurological MEchanismS of Injury, and Sleep-like cellular dynamics (NEMESIS) (ref. 101071900) funded by the EU ERC Synergy Horizon Europe; the NODYN Project PID2022-136216NB-I00 financed by the MCIN/AEI/10.13039/501100011033/FEDER, UE., the Ministry of Science and Innovation, the State Research Agency and the European Regional Development Fund; the AGAUR research support grant (ref. 2021 SGR 00917) funded by the Department of Research and Universities of the Generalitat of Catalunya, and the project eBRAIN-Health - Actionable Multilevel Health Data (id 101058516), funded by the EU Horizon Europe. This work was supported by the Virtual Research Environment at the Charité Berlin and EBRAINS Health Data Cloud operated by the Charité Universitätsmedizin Berlin for PR. PR also acknowledges support by Digital Europe TEF-Health 101100700, EU H2020 Virtual Brain Cloud 826421, Human Brain Project SGA2 785907; Human Brain Project SGA3 945539, ERC Consolidator 683049; German Research Foundation SFB 1436 (project ID 425899996); SFB 1315 (project ID 327654276); SFB 936 (project ID 178316478; SFB-TRR 295 (project ID 424778381); SPP Computational Connectomics RI 2073/6-1, RI 2073/10-2, RI 2073/9-1; PHRASE Horizon EIC grant 101058240; Berlin Institute of Health & Foundation Charité, Johanna Quandt Excellence Initiative; ERAPerMed Pattern-Cog. ERA (ERAPERMED2021-127).
• dc.format.mimetype application/pdf
• dc.identifier.citation Patow G, Stefanovski L, Ritter P, Deco G, Kobeleva X. Whole-brain modeling of the differential influences of amyloid-beta and tau in Alzheimer's disease. Alzheimers Res Ther. 2023;15:210. DOI: 10.1186/s13195-023-01349-9
• dc.identifier.doi http://dx.doi.org/10.1186/s13195-023-01349-9
• dc.identifier.issn 1758-9193
• dc.identifier.uri http://hdl.handle.net/10230/70029
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Alzheimer's Research & Therapy. 2023 Dec;15:210
• dc.relation.isreferencedby http://dx.doi.org/10.6084/m9.figshare.26649606.v1
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/826421
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/785907
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/945539
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101071900
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/683049
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-122136OB-C22
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-136216NB-I00
• dc.rights This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Alzheimer’s disease
• dc.subject.keyword Amyloid-beta
• dc.subject.keyword Tau
• dc.subject.keyword Whole-brain model
• dc.subject.keyword Simulation
• dc.title Whole-brain modeling of the differential influences of amyloid-beta and tau in Alzheimer's disease
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion