Bulai Iulia Martina, Ferraresso Francesco, Gladiali Francesca
Department of Chemical, Physical, Mathematical and Natural Sciences, Via Vienna 2, 07100, Sassari, Italy.
Department of Mathematics "Giuseppe Peano", University of Torino, via Carlo Alberto 10, 10123, Torino, Italy.
J Math Biol. 2025 Aug 8;91(3):27. doi: 10.1007/s00285-025-02256-3.
The aggregation and accumulation of oligomers of misfolded Aβ-amyloids in the human brain is one of the possible causes for the onset of the Alzheimer's disease in the early stage. We introduce and study a new ODE model for the evolution of Alzheimer's disease based on the interaction between monomers, proto-oligomers, and oligomers of Aβ amyloid protein in a small portion of the human brain, based upon biochemical processes such as polymerization, depolymerization, fragmentation and concatenation. We further introduce the possibility of controlling the evolution of the system via a treatment that targets the monomers and/or the oligomers. We observe that a combined optimal treatment on both monomers and oligomers induces a substantial decrease of the oligomer concentration at the final stage. A single treatment on oligomers performs better than a single treatment on monomers. These results shed a light on the effectiveness of immunotherapy using anti-Aβ antibodies, targeting monomers or oligomers. Several numerical simulations show how the oligomer concentration evolves without treatment, with single monomer/oligomer treatment, or with a combined treatment.
人脑中错误折叠的Aβ淀粉样蛋白寡聚体的聚集和积累是早期阿尔茨海默病发病的可能原因之一。我们基于人脑中一小部分区域内Aβ淀粉样蛋白单体、原寡聚体和寡聚体之间的相互作用，引入并研究了一种新的阿尔茨海默病演化常微分方程模型，该模型基于诸如聚合、解聚、碎片化和连接等生化过程。我们进一步介绍了通过针对单体和/或寡聚体的治疗来控制系统演化的可能性。我们观察到，对单体和寡聚体进行联合优化治疗会使最终阶段的寡聚体浓度大幅降低。对寡聚体进行单一治疗比对单体进行单一治疗效果更好。这些结果揭示了使用抗Aβ抗体针对单体或寡聚体进行免疫治疗的有效性。几个数值模拟展示了在不进行治疗、进行单体/寡聚体单一治疗或进行联合治疗的情况下，寡聚体浓度是如何演化的。
