{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:14:47Z","timestamp":1783433687754,"version":"3.54.6"},"reference-count":92,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072000"],"award-info":[{"award-number":["82072000"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["YQ2023H016"],"award-info":[{"award-number":["YQ2023H016"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012476","name":"Fundamental Research Funds for Central Universities of the Central South University","doi-asserted-by":"publisher","award":["HIT.OCEF.2013015"],"award-info":[{"award-number":["HIT.OCEF.2013015"]}],"id":[{"id":"10.13039\/501100012476","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Neurodegenerative diseases are a group of disorders characterized by progressive degeneration or death of neurons. The complexity of clinical symptoms and irreversibility of disease progression significantly affects individual lives, leading to premature mortality. The prevalence of neurodegenerative diseases keeps increasing, yet the specific pathogenic mechanisms remain incompletely understood and effective treatment strategies are lacking. In recent years, convergent experimental evidence supports the \u201cprion-like transmission\u201d assumption that abnormal proteins induce misfolding of normal proteins, and these misfolded proteins propagate throughout the neural networks to cause neuronal death. To elucidate this dynamic process in vivo from a computational perspective, researchers have proposed three connectome-based biophysical models to simulate the spread of pathological proteins: the Network Diffusion Model, the Epidemic Spreading Model, and the agent-based Susceptible-Infectious-Removed model. These models have demonstrated promising predictive capabilities. This review focuses on the explanations of their fundamental principles and applications. Then, we compare the strengths and weaknesses of the models. Building upon this foundation, we introduce new directions for model optimization and propose a unified framework for the evaluation of connectome-based biophysical models. We expect that this review could lower the entry barrier for researchers in this field, accelerate model optimization, and thereby advance the clinical translation of connectome-based biophysical models.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012743","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T18:25:40Z","timestamp":1737483940000},"page":"e1012743","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Connectome-based biophysical models of pathological protein spreading in neurodegenerative 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Von Smoluchowski","year":"1918","journal-title":"Zeitschrift f\u00fcr Physikalische Chemie."},{"issue":"3","key":"pcbi.1012743.ref035","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00285-023-01985-7","article-title":"The role of A[Formula: see text] and Tau proteins in Alzheimer\u2019s disease: a mathematical model on graphs","volume":"87","author":"M Bertsch","year":"2023","journal-title":"J Math Biol"},{"key":"pcbi.1012743.ref036","doi-asserted-by":"crossref","first-page":"1321171","DOI":"10.3389\/fphar.2024.1321171","article-title":"On propagation in networks, promising models beyond network diffusion to describe degenerative brain diseases and traumatic brain injuries","volume":"15","author":"D Vergni","year":"2024","journal-title":"Front Pharmacol"},{"key":"pcbi.1012743.ref037","article-title":"Connectome-mediated prediction of future tau-PET burden in Alzheimer\u2019s disease.","author":"PF Damasceno","year":"2020","journal-title":"Cold Spring Harbor Laboratory."},{"issue":"6","key":"pcbi.1012743.ref038","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.jalz.2017.11.014","article-title":"Regional vulnerability in Alzheimer\u2019s disease: The role of cell-autonomous and transneuronal processes.","volume":"14","author":"D Acosta","year":"2018","journal-title":"Alzheimers Dement."},{"key":"pcbi.1012743.ref039","first-page":"384","article-title":"A longitudinal model for tau aggregation in Alzheimer\u2019s disease based on structural connectivity.","volume":"11492","author":"F Yang","year":"2019","journal-title":"Inf Process Med Imaging"},{"issue":"7465","key":"pcbi.1012743.ref040","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nature12481","article-title":"Self-propagation of pathogenic protein aggregates in neurodegenerative diseases","volume":"501","author":"M Jucker","year":"2013","journal-title":"Nature"},{"issue":"6","key":"pcbi.1012743.ref041","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.neuron.2012.03.004","article-title":"Predicting regional neurodegeneration from the healthy brain functional connectome","volume":"73","author":"J Zhou","year":"2012","journal-title":"Neuron"},{"issue":"4","key":"pcbi.1012743.ref042","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1007\/s11065-009-9118-x","article-title":"Beta-amyloid deposition and the aging brain","volume":"19","author":"KM Rodrigue","year":"2009","journal-title":"Neuropsychol Rev"},{"key":"pcbi.1012743.ref043","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1196\/annals.1297.005","article-title":"The biphasic relationship between regional brain senile plaque and neurofibrillary tangle distributions: modification by age, sex, and APOE polymorphism","volume":"1019","author":"EH Corder","year":"2004","journal-title":"Ann N Y Acad Sci"},{"key":"pcbi.1012743.ref044","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3389\/fnagi.2013.00055","article-title":"Biomarker-based prediction of progression in MCI: Comparison of AD signature and hippocampal volume with spinal fluid amyloid-\u03b2 and tau.","volume":"5","author":"BC Dickerson","year":"2013","journal-title":"Front Aging Neurosci."},{"issue":"3","key":"pcbi.1012743.ref045","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.neurobiolaging.2013.08.027","article-title":"Effects of cerebrospinal fluid proteins on brain atrophy rates in cognitively healthy older adults","volume":"35","author":"N Mattsson","year":"2014","journal-title":"Neurobiol Aging"},{"issue":"Pt 7","key":"pcbi.1012743.ref046","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1093\/brain\/aws127","article-title":"Apolipoprotein E4 effects in Alzheimer\u2019s disease are mediated by synaptotoxic oligomeric amyloid-\u03b2","volume":"135","author":"RM Koffie","year":"2012","journal-title":"Brain"},{"issue":"16","key":"pcbi.1012743.ref047","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","article-title":"Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. 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Waters","year":"2010","journal-title":"The concentration of soluble extracellular amyloid-\u03b2 protein in acute brain slices from CRND"},{"issue":"1","key":"pcbi.1012743.ref054","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/s42003-021-02133-x","article-title":"Integrating molecular, histopathological, neuroimaging and clinical neuroscience data with NeuroPM-box","volume":"4","author":"Y Iturria-Medina","year":"2021","journal-title":"Commun Biol"},{"issue":"5","key":"pcbi.1012743.ref055","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1038\/s41591-021-01309-6","article-title":"Four distinct trajectories of tau deposition identified in Alzheimer\u2019s disease","volume":"27","author":"JW Vogel","year":"2021","journal-title":"Nat Med"},{"issue":"3","key":"pcbi.1012743.ref056","doi-asserted-by":"crossref","first-page":"fcac085","DOI":"10.1093\/braincomms\/fcac085","article-title":"Differentiating amyloid beta spread in autosomal dominant and sporadic Alzheimer\u2019s disease","volume":"4","author":"E Levitis","year":"2022","journal-title":"Brain Commun"},{"key":"pcbi.1012743.ref057","doi-asserted-by":"crossref","DOI":"10.1101\/2020.12.18.423469","article-title":"Leveraging selective hippocampal vulnerability among Alzheimer\u2019s disease subtypes reveals a novel tau binding partner SERPINA5.","author":"AM Crist","year":"2020"},{"issue":"6","key":"pcbi.1012743.ref058","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1007\/s00401-017-1691-0","article-title":"Proteomic differences in amyloid plaques in rapidly progressive and sporadic Alzheimer\u2019s disease","volume":"133","author":"E Drummond","year":"2017","journal-title":"Acta Neuropathol"},{"key":"pcbi.1012743.ref059","first-page":"66","article-title":"Spread of epidemic disease on networks","author":"ME Newman","year":"2002","journal-title":"Phys Rev E Stat Nonlin Soft Matter 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Shafiei","year":"2023","journal-title":"Brain"},{"issue":"9","key":"pcbi.1012743.ref063","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1093\/brain\/awac187","article-title":"Brain atrophy in prodromal synucleinopathy is shaped by structural connectivity and gene expression","volume":"145","author":"S Rahayel","year":"2022","journal-title":"Brain"},{"issue":"Pt 4","key":"pcbi.1012743.ref064","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1093\/brain\/awt037","article-title":"Prion-like spreading of pathological \u03b1-synuclein in brain","volume":"136","author":"M Masuda-Suzukake","year":"2013","journal-title":"Brain"},{"issue":"9","key":"pcbi.1012743.ref065","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1016\/j.neurobiolaging.2011.06.022","article-title":"Prion-like acceleration of a synucleinopathy in a transgenic mouse model","volume":"33","author":"AL Mougenot","year":"2012","journal-title":"Neurobiol 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Recasens","year":"2014","journal-title":"Ann Neurol"},{"issue":"1","key":"pcbi.1012743.ref069","doi-asserted-by":"crossref","first-page":"21170","DOI":"10.1038\/s41598-022-25131-3","article-title":"The effects of microglia on tauopathy progression can be quantified using Nexopathy in silico (Nexis) models.","volume":"12","author":"C Anand","year":"2022","journal-title":"Sci Rep."},{"issue":"8","key":"pcbi.1012743.ref070","doi-asserted-by":"crossref","first-page":"e0135247","DOI":"10.1371\/journal.pone.0135247","article-title":"Reproducibility of the Structural Brain Connectome Derived from Diffusion Tensor Imaging.","volume":"10","author":"L Bonilha","year":"2015","journal-title":"PLoS ONE"},{"issue":"4","key":"pcbi.1012743.ref071","doi-asserted-by":"crossref","first-page":"045004","DOI":"10.1088\/1741-2552\/ab947b","article-title":"Connectomic consistency: a systematic stability analysis of structural and functional connectivity","volume":"17","author":"Y 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Michiels","year":"2021","journal-title":"Neuroimage."},{"key":"pcbi.1012743.ref080","doi-asserted-by":"crossref","first-page":"119771","DOI":"10.1016\/j.neuroimage.2022.119771","article-title":"Identification of pre-synaptic density networks using [(11)C]UCB-J PET imaging and ICA in mice.","volume":"264","author":"J Akkermans","year":"2022","journal-title":"Neuroimage."},{"key":"pcbi.1012743.ref081","doi-asserted-by":"crossref","first-page":"102089","DOI":"10.1016\/j.pneurobio.2021.102089","article-title":"Glucose metabolic crosstalk and regulation in brain function and diseases","volume":"204","author":"S Zhang","year":"2021","journal-title":"Prog Neurobiol"},{"issue":"8","key":"pcbi.1012743.ref082","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1177\/0271678X20982382","article-title":"Regional and depth-dependence of cortical blood-flow assessed with high-resolution Arterial Spin Labeling (ASL).","volume":"41","author":"M Taso","year":"2021","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1","key":"pcbi.1012743.ref083","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1073\/pnas.89.1.212","article-title":"Magnetic resonance imaging of perfusion using spin inversion of arterial water","volume":"89","author":"DS Williams","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"41","key":"pcbi.1012743.ref084","doi-asserted-by":"crossref","first-page":"17757","DOI":"10.1073\/pnas.1010459107","article-title":"Regional aerobic glycolysis in the human brain","volume":"107","author":"SN Vaishnavi","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"pcbi.1012743.ref085","doi-asserted-by":"crossref","first-page":"7653","DOI":"10.1002\/jcp.29682","article-title":"Glucose, glycolysis, and neurodegenerative diseases","volume":"235","author":"BL Tang","year":"2020","journal-title":"J Cell 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