Patow, GustavoStefanovski, LeonRitter, PetraDeco, GustavoKobeleva, Xenia2025-03-272025-03-272023Patow 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/s13195-023-01349-91758-9193http://hdl.handle.net/10230/70029Includes supplementary materials for the online appendix.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.application/pdfengThis 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s13195-023-01349-9Alzheimer’s diseaseAmyloid-betaTauWhole-brain modelSimulationinfo:eu-repo/semantics/openAccess