{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:11:00Z","timestamp":1792253460538,"version":"4.4.0"},"reference-count":105,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003398","name":"Shanxi Scholarship Council of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003398","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Theoretical Biology"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1016\/j.jtbi.2026.112425","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T17:21:53Z","timestamp":1773249713000},"page":"112425","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Optimal control of Alzheimer\u2019s disease model via multi-target combination therapy"],"prefix":"10.1016","volume":"625","author":[{"given":"Mingyan","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zun-Guang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.jtbi.2026.112425_bib0001","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1080\/17513758.2020.1869843","article-title":"A continuous-time mathematical model and discrete approximations for the aggregation of \u03b2-amyloid","volume":"15","author":"Ackleh","year":"2021","journal-title":"J. Biol. Dyn."},{"issue":"3","key":"10.1016\/j.jtbi.2026.112425_bib0002","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.biosystems.2013.06.004","article-title":"Optimal isolation control strategies and cost-effectiveness analysis of a two-strain avian influenza model","volume":"113","author":"Agusto","year":"2013","journal-title":"Biosyst"},{"key":"10.1016\/j.jtbi.2026.112425_bib0003","first-page":"161","article-title":"Optimal control and cost-effective analysis of the 2017 meningitis outbreak in nigeria","volume":"4","author":"Agusto","year":"2019","journal-title":"Infect. Dis. Model."},{"key":"10.1016\/j.jtbi.2026.112425_bib0004","unstructured":"Alzheimer\u2019s Disease Neuroimaging Initiative, 2022. Alzheimer\u2019s disease neuroimaging initiative homepage. https:\/\/adni.loni.usc.edu."},{"issue":"4","key":"10.1016\/j.jtbi.2026.112425_bib0005","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/S1474-4422(19)30435-1","article-title":"Interpretation of risk loci from genome-wide association studies of alzheimer\u2019s disease","volume":"19","author":"Andrews","year":"2020","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.jtbi.2026.112425_bib0006","doi-asserted-by":"crossref","DOI":"10.1016\/j.chaos.2020.110237","article-title":"Backward bifurcation and sensitivity analysis for bacterial meningitis transmission dynamics with a nonlinear recovery rate","volume":"140","author":"Asamoah","year":"2020","journal-title":"Chaos Solitons Fract."},{"key":"10.1016\/j.jtbi.2026.112425_bib0007","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.11182","article-title":"Sampling the conformational space of the catalytic subunit of human \u03b3-secretase","volume":"4","author":"Bai","year":"2015","journal-title":"ELife"},{"issue":"7","key":"10.1016\/j.jtbi.2026.112425_bib0008","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.tips.2020.04.008","article-title":"A perspective on multi-target drugs for alzheimer\u2019s disease","volume":"41","author":"Benek","year":"2020","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.jtbi.2026.112425_bib0009","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nature11691","article-title":"Automated design of ligands to polypharmacological profiles","volume":"492","author":"Besnard","year":"2012","journal-title":"Nature"},{"issue":"9","key":"10.1016\/j.jtbi.2026.112425_bib0010","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.tins.2008.06.005","article-title":"Neuronal calcium mishandling and the pathogenesis of alzheimer\u2019s disease","volume":"31","author":"Bezprozvanny","year":"2008","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.jtbi.2026.112425_bib0011","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jtbi.2013.04.015","article-title":"The progression towards alzheimer\u2019s disease described as a bistable switch arising from the positive loop between amyloids and ca2+","volume":"331","author":"Caluw\u00e9","year":"2013","journal-title":"J. Theor. Biol."},{"issue":"2","key":"10.1016\/j.jtbi.2026.112425_bib0012","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.tins.2020.10.004","article-title":"Mitochondria and calcium in alzheimer\u2019s disease: from cell signaling to neuronal cell death","volume":"44","author":"Calvo-Rodriguez","year":"2021","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.jtbi.2026.112425_bib0013","doi-asserted-by":"crossref","first-page":"4100","DOI":"10.1007\/s11538-019-00642-9","article-title":"Modeling public health campaigns for sexually transmitted infections via optimal and feedback control","volume":"81","author":"Camacho","year":"2019","journal-title":"Bull. Math. Biol."},{"key":"10.1016\/j.jtbi.2026.112425_bib0014","first-page":"3254","article-title":"Fast state estimations for large distribution systems using deep neural networks as surrogate","volume":"5","author":"Cao","year":"2020","journal-title":"IEEE PES General Meeting"},{"key":"10.1016\/j.jtbi.2026.112425_bib0015","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-09692-y","article-title":"Network-based prediction of drug combinations","volume":"10","author":"Cheng","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jtbi.2026.112425_bib0016","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1007\/s11538-008-9299-0","article-title":"Determining important parameters in the spread of malaria through the sensitivity analysis of a mathematical model","volume":"70","author":"Chitnis","year":"2008","journal-title":"Bull. Math. Biol."},{"issue":"9","key":"10.1016\/j.jtbi.2026.112425_bib0017","first-page":"793","article-title":"A new initiative on precision medicine. new engl","volume":"372","author":"Collins","year":"2015","journal-title":"J. Med."},{"issue":"1","key":"10.1016\/j.jtbi.2026.112425_bib0018","article-title":"Alzheimer\u2019s disease drug development pipeline: 2021","volume":"7","author":"Cummings","year":"2021","journal-title":"Alzheimers Dement. Transl. Res. Clin. Interv."},{"issue":"17","key":"10.1016\/j.jtbi.2026.112425_bib0019","doi-asserted-by":"crossref","first-page":"12463","DOI":"10.1074\/jbc.R109.080895","article-title":"Calcium signaling and amyloid toxicity in alzheimer disease","volume":"285","author":"Demuro","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jtbi.2026.112425_bib0020","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41586-023-06120-6","article-title":"Myelin dysfunction drives amyloid-\u03b2 deposition in models of alzheimer\u2019s disease","volume":"618","author":"Depp","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.jtbi.2026.112425_bib0021","doi-asserted-by":"crossref","DOI":"10.1016\/j.aml.2024.109407","article-title":"A study in alzheimer\u2019s disease model for pathological effect of oligomers on the interplay between \u03b2-amyloid and ca2+","volume":"163","author":"Dong","year":"2025","journal-title":"Appl. Math. Lett."},{"issue":"1","key":"10.1016\/j.jtbi.2026.112425_bib0022","first-page":"65","article-title":"Adaptive designs for clinical trials. new engl","volume":"375","author":"Drazen","year":"2016","journal-title":"J. Med."},{"issue":"2","key":"10.1016\/j.jtbi.2026.112425_bib0023","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.cell.2020.12.036","article-title":"Breathing new life into the rational design of alzheimer\u2019s therapeutics","volume":"184","author":"Dries","year":"2020","journal-title":"Cell"},{"issue":"1-2","key":"10.1016\/j.jtbi.2026.112425_bib0024","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0025-5564(02)00108-6","article-title":"Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission","volume":"180","author":"Driessche","year":"2002","journal-title":"Math. Biosci."},{"issue":"1","key":"10.1016\/j.jtbi.2026.112425_bib0025","first-page":"9","article-title":"Lecanemab in early alzheimer\u2019s disease. new engl","volume":"388","author":"Dyck","year":"2023","journal-title":"J. Med."},{"issue":"16","key":"10.1016\/j.jtbi.2026.112425_bib0026","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1001\/jama.1996.03530400035035","article-title":"Cost-effectiveness of the transdermal nicotine patch as an adjunct to physicians\u2019 smoking cessation counseling","volume":"275","author":"Fiscella","year":"1996","journal-title":"JAMA"},{"issue":"7","key":"10.1016\/j.jtbi.2026.112425_bib0027","doi-asserted-by":"crossref","first-page":"605","DOI":"10.7326\/0003-4819-125-7-199610010-00011","article-title":"Surrogate end points in clinical trials: are we being misled?","volume":"125","author":"Fleming","year":"1996","journal-title":"Ann. Intern. Med."},{"issue":"3","key":"10.1016\/j.jtbi.2026.112425_bib0028","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1093\/brain\/123.3.484","article-title":"Atypical and typical presentations of alzheimer\u2019s disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases","volume":"123","author":"Galton","year":"2000","journal-title":"Brain"},{"key":"10.1016\/j.jtbi.2026.112425_bib0029","doi-asserted-by":"crossref","first-page":"13513","DOI":"10.1007\/s11071-023-08547-y","article-title":"A confidence ellipse analysis for stochastic dynamics model of Alzheimer\u2019s disease","volume":"111","author":"Gao","year":"2023","journal-title":"Nonlinear Dyn."},{"issue":"4","key":"10.1016\/j.jtbi.2026.112425_bib0030","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1073\/pnas.87.4.1461","article-title":"Minimal model for signal-induced ca2 oscillations and for their frequency encoding through protein phosphorylation","volume":"87","author":"Goldbeter","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"2","key":"10.1016\/j.jtbi.2026.112425_bib0031","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.neuron.2008.07.013","article-title":"Linking calcium to a\u03b2 and alzheimer\u2019s disease","volume":"59","author":"Green","year":"2008","journal-title":"Neuron"},{"key":"10.1016\/j.jtbi.2026.112425_bib0032","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/359322a0","article-title":"Amyloid \u03b2-peptide is produced by cultured cells during normal metabolism","volume":"359","author":"Haass","year":"1992","journal-title":"Nature"},{"key":"10.1016\/j.jtbi.2026.112425_bib0033","doi-asserted-by":"crossref","first-page":"5481","DOI":"10.1038\/s41380-021-01249-0","article-title":"The amyloid-\u03b2 pathway in alzheimer\u2019s disease","volume":"26","author":"Hampel","year":"2021","journal-title":"Mol. Psychiatr."},{"issue":"9","key":"10.1016\/j.jtbi.2026.112425_bib0034","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1010481","article-title":"Optimal anti-amyloid-beta therapy for alzheimer\u2019s disease via a personalized mathematical model","volume":"18","author":"Hao","year":"2022","journal-title":"PLoS Comput. Biol."},{"issue":"5054","key":"10.1016\/j.jtbi.2026.112425_bib0035","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1126\/science.1566067","article-title":"Alzheimer\u2019s disease: the amyloid cascade hypothesis","volume":"256","author":"Hardy","year":"1992","journal-title":"Science"},{"issue":"9","key":"10.1016\/j.jtbi.2026.112425_bib0036","first-page":"775","article-title":"Toward gerineuropalliative care for patients with dementia. new engl","volume":"389","author":"Harrison","year":"2023","journal-title":"J. Med."},{"key":"10.1016\/j.jtbi.2026.112425_bib0037","doi-asserted-by":"crossref","DOI":"10.1016\/j.ceca.2024.102929","article-title":"Septin regulation of orai-mediated ca2+ entry - a novel target for neurodegeneration","volume":"123","author":"Hasan","year":"2024","journal-title":"Cell Calcium"},{"key":"10.1016\/j.jtbi.2026.112425_bib0038","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00285-018-1267-1","article-title":"Stability analysis of a steady state of a model describing alzheimer\u2019s disease and interactions with prion proteins","volume":"78","author":"Helal","year":"2019","journal-title":"J. Math. Biol."},{"key":"10.1016\/j.jtbi.2026.112425_bib0039","doi-asserted-by":"crossref","DOI":"10.1016\/j.aml.2022.108308","article-title":"Analysis of a stochastic reaction-diffusion alzheimer\u2019s disease system driven by space-time white noise","volume":"134","author":"Hu","year":"2022","journal-title":"Appl. Math. Lett."},{"issue":"7831","key":"10.1016\/j.jtbi.2026.112425_bib0040","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/s41586-020-2681-2","article-title":"The innate immunity protein ifitm3 modulates \u03b3-secretase in alzheimer\u2019s disease","volume":"586","author":"Hur","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.jtbi.2026.112425_bib0041","doi-asserted-by":"crossref","DOI":"10.1016\/j.jtbi.2024.111814","article-title":"A\u03b2-protein polymerization in alzheimer disease: optimal control for nucleation parameter estimation","volume":"589","author":"Ionel","year":"2024","journal-title":"J. Theor. Biol."},{"issue":"8","key":"10.1016\/j.jtbi.2026.112425_bib0042","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1523\/JNEUROSCI.2039-21.2021","article-title":"Presenilin involved in alzheimer\u2019s disease pathogenesis","volume":"42","author":"Islam","year":"2022","journal-title":"J. Neurosci."},{"issue":"1","key":"10.1016\/j.jtbi.2026.112425_bib0043","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S1474-4422(09)70299-6","article-title":"Hypothetical model of dynamic biomarkers of the alzheimer\u2019s pathological cascade","volume":"9","author":"Jack","year":"2010","journal-title":"Lancet Neurol."},{"issue":"8","key":"10.1016\/j.jtbi.2026.112425_bib0044","first-page":"712","article-title":"Biomarker changes during 20 years preceding alzheimer\u2019s disease. new engl","volume":"390","author":"Jia","year":"2024","journal-title":"J. Med."},{"issue":"4","key":"10.1016\/j.jtbi.2026.112425_bib0045","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jalz.2017.12.006","article-title":"The cost of alzheimer\u2019s disease in china and re-estimation of costs worldwide","volume":"14","author":"Jia","year":"2018","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.jtbi.2026.112425_bib0046","article-title":"The affordability of lecanemab, an amyloid-targeting therapy for alzheimer\u2019s disease: an eadc-ec viewpoint","volume":"29","author":"J\u00f6nsson","year":"2023","journal-title":"Lancet Reg. Health Eur."},{"issue":"4","key":"10.1016\/j.jtbi.2026.112425_bib0047","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/oca.710","article-title":"Optimal control of an","volume":"23","author":"Joshi","year":"2002","journal-title":"HIV immunology model. Optim. Contr. Appl. Met."},{"key":"10.1016\/j.jtbi.2026.112425_bib0048","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/nrd3505","article-title":"The amyloid cascade hypothesis for alzheimer\u2019s disease: an appraisal for the development of therapeutics","volume":"10","author":"Karran","year":"2011","journal-title":"Nat. Rev. Drug. Discov."},{"issue":"2","key":"10.1016\/j.jtbi.2026.112425_bib0049","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jalz.2016.12.006","article-title":"Calcium hypothesis of alzheimer\u2019s disease and brain aging: a framework for integrating new evidence into a comprehensive theory of pathogenesis","volume":"13","author":"Khachaturian","year":"2017","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.jtbi.2026.112425_bib0050","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-12683-8","article-title":"Cryo-em structure and polymorphism of a\u03b2 amyloid fibrils purified from alzheimer\u2019s brain tissue","volume":"10","author":"Kollmer","year":"2019","journal-title":"Nat. Commun."},{"issue":"2","key":"10.1016\/j.jtbi.2026.112425_bib0051","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.neuron.2008.06.008","article-title":"A\u03b2 plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks","volume":"59","author":"Kuchibhotla","year":"2008","journal-title":"Neuron"},{"issue":"3","key":"10.1016\/j.jtbi.2026.112425_bib0052","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1137\/060665294","article-title":"Antiangiogenic therapy in cancer treatment as an optimal control problem","volume":"46","author":"Ledzewicz","year":"2007","journal-title":"SIAM J. Control Optim."},{"key":"10.1016\/j.jtbi.2026.112425_bib0053","series-title":"Optimal Control Applied to Biological Models","author":"Lenhart","year":"2007"},{"issue":"18","key":"10.1016\/j.jtbi.2026.112425_bib0054","first-page":"1762","article-title":"Progress with treatments for alzheimer\u2019s disease. new engl","volume":"384","author":"Levey","year":"2021","journal-title":"J. Med"},{"key":"10.1016\/j.jtbi.2026.112425_bib0055","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/78078","article-title":"Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (p301l) tau protein","volume":"25","author":"Lewis","year":"2000","journal-title":"Nat. Genet."},{"key":"10.1016\/j.jtbi.2026.112425_bib0056","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cell.2025.06.035","article-title":"Cell-type-directed network-correcting combination therapy for alzheimer\u2019s disease","volume":"188","author":"Li","year":"2025","journal-title":"Cell"},{"key":"10.1016\/j.jtbi.2026.112425_bib0057","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein e and alzheimer disease: risk, mechanisms and therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.jtbi.2026.112425_bib0058","article-title":"History and progress of hypotheses and clinical trials for alzheimer\u2019s disease","volume":"4","author":"Liu","year":"2019","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.jtbi.2026.112425_bib0059","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0140-6736(24)01296-0","article-title":"Dementia prevention, intervention, and care: 2024 report of the lancet standing commission","volume":"404","author":"Livingston","year":"2024","journal-title":"Lancet"},{"issue":"2","key":"10.1016\/j.jtbi.2026.112425_bib0060","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","article-title":"Alzheimer disease: an update on pathobiology and treatment strategies","volume":"179","author":"Long","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.jtbi.2026.112425_bib0061","series-title":"An Introduction to Mathematical Epidemiology","author":"Martcheva","year":"2015"},{"key":"10.1016\/j.jtbi.2026.112425_bib0062","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s10589-011-9454-7","article-title":"Convergence of the forward-backward sweep method in optimal control","volume":"53","author":"Mcasey","year":"2012","journal-title":"Comput. Optim. Appl."},{"key":"10.1016\/j.jtbi.2026.112425_bib0063","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/s41557-020-0452-1","article-title":"Dynamics of oligomer populations formed during the aggregation of alzheimer\u2019s a\u03b242 peptide","volume":"12","author":"Michaels","year":"2020","journal-title":"Nat. Chem."},{"key":"10.1016\/j.jtbi.2026.112425_bib0064","doi-asserted-by":"crossref","first-page":"14593","DOI":"10.1073\/pnas.1904090116","article-title":"Optimal control strategies for inhibition of protein aggregation","volume":"15316","author":"Michaels","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"32","key":"10.1016\/j.jtbi.2026.112425_bib0065","doi-asserted-by":"crossref","first-page":"13293","DOI":"10.1073\/pnas.1109297108","article-title":"Constitutive camp response element binding protein (creb) activation by alzheimer\u2019s disease presenilin-driven inositol trisphosphate receptor (insp3r) ca2+ signaling","volume":"108","author":"M\u00fcller","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"5","key":"10.1016\/j.jtbi.2026.112425_bib0066","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nrn.2017.29","article-title":"Not just amyloid: physiological functions of the amyloid precursor protein family","volume":"18","author":"M\u00fcller","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.jtbi.2026.112425_bib0067","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S0140-6736(24)02352-3","article-title":"Population-health impact of new drugs recommended by the national institute for health and care excellence in england during 2000-20: a retrospective analysis","volume":"405","author":"Naci","year":"2025","journal-title":"Lancet"},{"key":"10.1016\/j.jtbi.2026.112425_bib0068","series-title":"Optimal Control Systems","author":"Naidu","year":"2003"},{"key":"10.1016\/j.jtbi.2026.112425_bib0069","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/nn0901-887","article-title":"The \u2018arctic\u2019 app mutation (e693g) causes alzheimer\u2019s disease by enhanced a\u03b2 protofibril formation","volume":"4","author":"Nilsberth","year":"2001","journal-title":"Nat. Neurosci."},{"issue":"6450","key":"10.1016\/j.jtbi.2026.112425_bib0070","doi-asserted-by":"crossref","DOI":"10.1126\/science.aav9518","article-title":"Amyloid \u03b2 oligomers constrict human capillaries in alzheimer\u2019s disease via signaling to pericytes","volume":"365","author":"Nortley","year":"2019","journal-title":"Science"},{"issue":"1","key":"10.1016\/j.jtbi.2026.112425_bib0071","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1080\/17513758.2020.1722265","article-title":"Modelling malaria dynamics with partial immunity and protected travellers: optimal control and cost-effectiveness analysis","volume":"14","author":"Olaniyi","year":"2020","journal-title":"J. Biol. Dyn."},{"issue":"4","key":"10.1016\/j.jtbi.2026.112425_bib0072","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1093\/brain\/aww015","article-title":"Cerebrospinal fluid analysis detects cerebral amyloid-\u03b2 accumulation earlier than positron emission tomography","volume":"139","author":"Palmqvist","year":"2016","journal-title":"Brain"},{"issue":"2","key":"10.1016\/j.jtbi.2026.112425_bib0073","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aau6328","article-title":"Sodium rutin ameliorates alzheimer\u2019s disease-like pathology by enhancing microglial amyloid-\u03b2 clearance","volume":"5","author":"Pan","year":"2019","journal-title":"Sci. Adv."},{"key":"10.1016\/j.jtbi.2026.112425_bib0074","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41582-020-0333-7","article-title":"Protein transmission in neurodegenerative disease","volume":"16","author":"Peng","year":"2020","journal-title":"Nat. Rev. Neurol."},{"issue":"2","key":"10.1016\/j.jtbi.2026.112425_bib0075","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1053\/j.gastro.2010.06.013","article-title":"Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment","volume":"139","author":"Pietrangelo","year":"2010","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jtbi.2026.112425_bib0076","series-title":"The Mathematical Theory of Optimal Processes","author":"Pontryagin","year":"1962"},{"issue":"6699","key":"10.1016\/j.jtbi.2026.112425_bib0077","doi-asserted-by":"crossref","DOI":"10.1126\/science.add6260","article-title":"Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of alzheimer\u2019s disease","volume":"384","author":"Princen","year":"2024","journal-title":"Science"},{"key":"10.1016\/j.jtbi.2026.112425_bib0078","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/s41593-024-01620-8","article-title":"Identification of senescent, trem2-expressing microglia in aging and alzheimer\u2019s disease model mouse brain","volume":"27","author":"Rachmian","year":"2024","journal-title":"Nat. Neurosci."},{"issue":"5","key":"10.1016\/j.jtbi.2026.112425_bib0079","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1001\/jamaneurol.2022.0315","article-title":"Cost-effectiveness of aducanumab and donanemab for early alzheimer disease in the us","volume":"79","author":"Ross","year":"2022","journal-title":"JAMA Neurol."},{"issue":"1","key":"10.1016\/j.jtbi.2026.112425_bib0080","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1001\/jamaneurol.2021.4161","article-title":"Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early alzheimer disease","volume":"79","author":"Salloway","year":"2022","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.jtbi.2026.112425_bib0081","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"issue":"7","key":"10.1016\/j.jtbi.2026.112425_bib0082","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1016\/j.cell.2017.11.014","article-title":"Structural basis for regulated proteolysis by the \u03b1-secretase adam10","volume":"171","author":"Seegar","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.jtbi.2026.112425_bib0083","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1038\/s41591-023-02505-2","article-title":"Emerging diagnostics and therapeutics for alzheimer disease","volume":"29","author":"Self","year":"2023","journal-title":"Nat. Med."},{"key":"10.1016\/j.jtbi.2026.112425_bib0084","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ress.2015.12.002","article-title":"The generalization of latin hypercube sampling","volume":"148","author":"Shields","year":"2016","journal-title":"Reliab. Eng. Syst. Saf."},{"issue":"4","key":"10.1016\/j.jtbi.2026.112425_bib0085","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","article-title":"The cellular phase of Alzheimer\u2019s disease","volume":"164","author":"Strooper","year":"2016","journal-title":"Cell"},{"issue":"2","key":"10.1016\/j.jtbi.2026.112425_bib0086","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.neuron.2013.08.035","article-title":"Adam10 missense mutations potentiate \u03b2-amyloid accumulation by impairing prodomain chaperone function","volume":"80","author":"Suh","year":"2013","journal-title":"Neuron"},{"issue":"1","key":"10.1016\/j.jtbi.2026.112425_bib0087","doi-asserted-by":"crossref","DOI":"10.1186\/2047-9158-2-6","article-title":"Traditional chinese medicine: a promising candidate for the treatment of alzheimer\u2019s disease","volume":"2","author":"Sun","year":"2013","journal-title":"Transl. Neurodegener"},{"issue":"2","key":"10.1016\/j.jtbi.2026.112425_bib0088","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ceca.2009.12.003","article-title":"Calcium, cellular aging, and selective neuronal vulnerability in parkinson\u2019s disease","volume":"47","author":"Surmeier","year":"2010","journal-title":"Cell Calcium"},{"issue":"5","key":"10.1016\/j.jtbi.2026.112425_bib0089","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1074\/jbc.RA118.005222","article-title":"The trans-golgi network is a major site for \u03b1-secretase processing of amyloid precursor protein in primary neurons","volume":"294","author":"Tan","year":"2019","journal-title":"J. Biol. Chem."},{"issue":"9","key":"10.1016\/j.jtbi.2026.112425_bib0090","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S1474-4422(21)00214-3","article-title":"Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in alzheimer\u2019s disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study","volume":"20","author":"Thijssen","year":"2021","journal-title":"Lancet Neurol."},{"issue":"7","key":"10.1016\/j.jtbi.2026.112425_bib0091","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.tips.2024.05.005","article-title":"Multi-target drugs for alzheimer\u2019s disease","volume":"45","author":"Turgutalp","year":"2024","journal-title":"Trends Pharmacol. Sci."},{"issue":"10","key":"10.1016\/j.jtbi.2026.112425_bib0092","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41581-021-00430-6","article-title":"Hypertension-induced cognitive impairment: from pathophysiology to public health","volume":"17","author":"Ungvari","year":"2021","journal-title":"Nat. Rev. Nephrol."},{"issue":"5","key":"10.1016\/j.jtbi.2026.112425_bib0093","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1002\/cpt.2422","article-title":"Model-informed drug development: connecting the dots with a totality of evidence mindset to advance therapeutics","volume":"110","author":"Venkatakrishnan","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"issue":"4","key":"10.1016\/j.jtbi.2026.112425_bib0094","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S1474-4422(13)70044-9","article-title":"Amyloid \u03b2 deposition, neurodegeneration, and cognitive decline in sporadic alzheimer\u2019s disease: a prospective cohort study","volume":"12","author":"Villemagne","year":"2013","journal-title":"Lancet Neurol."},{"issue":"2","key":"10.1016\/j.jtbi.2026.112425_bib0095","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00401-015-1386-3","article-title":"Amyloid \u03b2 oligomers in alzheimer\u2019s disease pathogenesis, treatment, and diagnosis","volume":"129","author":"Viola","year":"2015","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.jtbi.2026.112425_bib0096","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s41586-022-05440-3","article-title":"Medin co-aggregates with vascular amyloid-\u03b2 in alzheimer\u2019s disease","volume":"612","author":"Wagner","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.jtbi.2026.112425_bib0097","doi-asserted-by":"crossref","DOI":"10.1007\/s11538-023-01205-9","article-title":"Towards optimal control of amyloid fibrillation","volume":"85","author":"Wang","year":"2023","journal-title":"Bull. Math. Biol."},{"issue":"6","key":"10.1016\/j.jtbi.2026.112425_bib0098","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1012165","article-title":"Threshold-awareness in adaptive cancer therapy","volume":"20","author":"Wang","year":"2024","journal-title":"PLoS Comput. Biol."},{"key":"10.1016\/j.jtbi.2026.112425_bib0099","unstructured":"World Health Organization, 2021. The top 10 causes of death. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/the-top-10-causes-of-death."},{"issue":"86","key":"10.1016\/j.jtbi.2026.112425_bib0100","doi-asserted-by":"crossref","DOI":"10.1098\/rsif.2012.1018","article-title":"Sensitivity analysis of infectious disease models: methods, advances and their application","volume":"10","author":"Wu","year":"2013","journal-title":"J. R. Soc. Interface"},{"issue":"2","key":"10.1016\/j.jtbi.2026.112425_bib0101","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s43587-022-00337-2","article-title":"Activation of innate immune cgas-sting pathway contributes to alzheimer\u2019s pathogenesis in 5\u202f\u00d7\u202ffad mice","volume":"3","author":"Xie","year":"2023","journal-title":"Nat. Aging."},{"issue":"1","key":"10.1016\/j.jtbi.2026.112425_bib0102","article-title":"Recent advances in alzheimer\u2019s disease: mechanisms, clinical trials and new drug development strategies","volume":"9","author":"Zhang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.jtbi.2026.112425_bib0103","doi-asserted-by":"crossref","DOI":"10.1016\/j.chaos.2024.114867","article-title":"Analysis for a model incorporating \u03b3-secretase inhibitor to explore the mechanism of \u2018amyloid-\u03b2 rise","volume":"183","author":"Zhang","year":"2024","journal-title":"Chaos Solitons Fract."},{"key":"10.1016\/j.jtbi.2026.112425_bib0104","doi-asserted-by":"crossref","DOI":"10.1016\/j.chaos.2023.113875","article-title":"Interplays between different secretases in the generation of amyloid-\u03b2 lead to the emergence of \u2018amyloid-\u03b2 rise","volume":"174","author":"Zhang","year":"2023","journal-title":"Chaos Solitons Fract."},{"key":"10.1016\/j.jtbi.2026.112425_bib0105","doi-asserted-by":"crossref","DOI":"10.1016\/j.cnsns.2020.105347","article-title":"Mathematical analysis for stochastic model of alzheimer\u2019s disease","volume":"89","author":"Zhang","year":"2020","journal-title":"Commun. Nonlinear Sci. Numer. Simul."}],"container-title":["Journal of Theoretical Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022519326000500?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022519326000500?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:23:29Z","timestamp":1777451009000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022519326000500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":105,"alternative-id":["S0022519326000500"],"URL":"https:\/\/doi.org\/10.1016\/j.jtbi.2026.112425","relation":{},"ISSN":["0022-5193"],"issn-type":[{"value":"0022-5193","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Optimal control of Alzheimer\u2019s disease model via multi-target combination therapy","name":"articletitle","label":"Article Title"},{"value":"Journal of Theoretical Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jtbi.2026.112425","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"112425"}}