{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:50:38Z","timestamp":1791489038230,"version":"4.3.4"},"reference-count":87,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000084","name":"Directorate for Engineering","doi-asserted-by":"publisher","award":["1953323"],"award-info":[{"award-number":["1953323"]}],"id":[{"id":"10.13039\/100000084","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U19NS120384"],"award-info":[{"award-number":["U19NS120384"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Biomed Eng"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Brain aging is accompanied by progressive morphological and neurobiological changes, which are significantly accelerated in neurodegenerative diseases, such as Alzheimer\u2019s disease. Detecting and differentiating these changes early is crucial for diagnosis, treatment planning, and therapeutic development. In this work, we present a computational multiphysics framework that couples protein biomarker propagation with tissue-level atrophy to distinguish between cognitively normal aging, mild cognitive impairment, and Alzheimer\u2019s disease. Our model integrates a network-based simulation of amyloid beta and tau protein spread with a finite element model of brain mechanics to simulate longitudinal brain shape changes over 40 years. Notably, we observe that amyloid beta accumulation precedes tau-driven degeneration by over a decade, aligning with empirical biomarker studies. We also introduce several mechanomarkers which are quantitative metrics of brain morphology such as displacement, cortical thickness, curvature, and sulcal depth. They serve as quantitative measures of disease-specific deformation patterns. Our simulations predict that Alzheimer\u2019s disease accelerates cerebral atrophy by about 12 years relative to normal aging, with early divergence in medial temporal and occipital regions. Our findings identify cortical thickness and area stretch as early and sensitive markers to distinguish between healthy and abnormal aging. Spatially, the supramarginal gyrus and entorhinal cortex should be considered as regions of early vulnerability. These results underscore the potential of physics-informed computational models to improve early detection of neurodegeneration and guide the development of region- and stage-specific diagnostic tools.<\/jats:p>","DOI":"10.1007\/s10439-026-04059-z","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T13:17:42Z","timestamp":1774358262000},"page":"3685-3706","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alzheimer\u2019s Disease Accelerates Cerebral Atrophy by Over a Decade Compared to Healthy Aging"],"prefix":"10.1007","volume":"54","author":[{"given":"Shima","family":"Jalalian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Weickenmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"4059_CR1","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s12993-021-00179-9","volume":"17","author":"A Zia","year":"2021","unstructured":"Zia A, Pourbagher-Shahri AM, Farkhondeh T, Samarghandian S (2021) Molecular and cellular pathways contributing to brain aging. Behav. Brain Funct. 17:6","journal-title":"Behav. Brain Funct."},{"key":"4059_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2021.111575","volume":"200","author":"Y Blinkouskaya","year":"2021","unstructured":"Blinkouskaya Y, Ca\u00e7oilo A, Gollamudi T, Jalalian S, Weickenmeier J (2021) Brain aging mechanisms with mechanical manifestations. Mech. Ageing Develop. 200:111575","journal-title":"Mech. Ageing Develop."},{"key":"4059_CR3","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1093\/bmb\/ldp033","volume":"92","author":"IJ Deary","year":"2009","unstructured":"Deary IJ, Corley J, Gow AJ, Harris SE, Houlihan LM, Marioni RE, Penke L, Rafnsson SB, Starr JM (2009) Age-associated cognitive decline. British Med. Bullet. 92:135\u2013152","journal-title":"British Med. Bullet."},{"key":"4059_CR4","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/nature12481","volume":"501","author":"M Jucker","year":"2013","unstructured":"Jucker, M., and L. C. Walker. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature. 501:45\u201351, 2013.","journal-title":"Nature"},{"key":"4059_CR5","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1146\/annurev-neuro-071714-033828","volume":"38","author":"LC Walker","year":"2015","unstructured":"Walker LC, Jucker M (2015) Neurodegenerative diseases: expanding the prion concept. Ann. Rev. Neurosci. 38:87\u2013103","journal-title":"Ann. Rev. Neurosci."},{"key":"4059_CR6","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1212\/WNL.0000000000002923","volume":"87","author":"CR Jack Jr","year":"2016","unstructured":"Jack, C. R., Jr., D. A. Bennett, K. Blennow, M. C. Carrillo, H. H. Feldman, G. B. Frisoni, H. Hampel, W. J. Jagust, K. A. Johnson, D. S. Knopman, et al. A\/t\/n: An unbiased descriptive classification scheme for alzheimer disease biomarkers. Neurology. 87:539\u2013547, 2016.","journal-title":"Neurology"},{"key":"4059_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanhl.2024.07.013","volume":"5","author":"M Sch\u00f6ll","year":"2024","unstructured":"Sch\u00f6ll M, Verberk IM, Del Campo M, Delaby C, Therriault J, Chong JR, Palmqvist S, Alcolea D (2024) Challenges in the practical implementation of blood biomarkers for alzheimer\u2019s disease. Lancet Healthy Longevit. 5:100630","journal-title":"Lancet Healthy Longevit."},{"key":"4059_CR8","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1016\/j.jalz.2018.07.220","volume":"14","author":"LM Shaw","year":"2018","unstructured":"Shaw, L. M., J. Arias, K. Blennow, D. Galasko, J. L. Molinuevo, S. Salloway, S. Schindler, M. C. Carrillo, J. A. Hendrix, A. Ross, et al. Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of alzheimer\u2019s disease. Alzheimer\u2019s & Dementia. 14:1505\u20131521, 2018.","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"4059_CR9","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s13195-023-01314-6","volume":"15","author":"B Dubois","year":"2023","unstructured":"Dubois B, von Arnim CA, Burnie N, Bozeat S, Cummings J (2023) Biomarkers in alzheimer\u2019s disease: role in early and differential diagnosis and recognition of atypical variants. Alzheimer\u2019s Res. Ther. 15:175","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"4059_CR10","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.121.158101","volume":"121","author":"J Weickenmeier","year":"2018","unstructured":"Weickenmeier J, Kuhl E, Goriely A (2018) Multiphysics of prionlike diseases: progression and atrophy. Phys. Rev. Lett. 121:158101","journal-title":"Phys. Rev. Lett."},{"key":"4059_CR11","doi-asserted-by":"publisher","first-page":"20190356","DOI":"10.1098\/rsif.2019.0356","volume":"16","author":"S Fornari","year":"2019","unstructured":"Fornari S, Sch\u00e4fer A, Jucker M, Goriely A, Kuhl E (2019) Prion-like spreading of alzheimer\u2019s disease within the brain\u2019s connectome. J. Royal Soc. Interface 16:20190356","journal-title":"J. Royal Soc. Interface"},{"key":"4059_CR12","first-page":"193","volume":"34","author":"M Bertsch","year":"2017","unstructured":"Bertsch M, Franchi B, Marcello N, Tesi MC, Tosin A (2017) Alzheimer\u2019s disease: a mathematical model for onset and progression. Math. Med. Biol. J. IMA 34:193\u2013214","journal-title":"Math. Med. Biol. J. IMA"},{"key":"4059_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fmech.2021.705653","volume":"7","author":"Y Blinkouskaya","year":"2021","unstructured":"Blinkouskaya Y, Weickenmeier J (2021) Brain shape changes associated with cerebral atrophy in healthy aging and alzheimer\u2019s disease. Front. Mech. Eng. 7:705653","journal-title":"Front. Mech. Eng."},{"key":"4059_CR14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003956","volume":"10","author":"Y Iturria-Medina","year":"2014","unstructured":"Iturria-Medina Y, Sotero RC, Toussaint PJ, Evans AC, Initiative ADN (2014) Epidemic spreading model to characterize misfolded proteins propagation in aging and associated neurodegenerative disorders. PLoS Computat. Biol. 10:e1003956","journal-title":"PLoS Computat. Biol."},{"key":"4059_CR15","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/j.neuron.2011.12.040","volume":"73","author":"A Raj","year":"2012","unstructured":"Raj, A., A. Kuceyeski, and M. Weiner. A network diffusion model of disease progression in dementia. Neuron. 73:1204\u20131215, 2012.","journal-title":"Neuron"},{"key":"4059_CR16","doi-asserted-by":"publisher","first-page":"371","DOI":"10.14283\/jpad.2021.23","volume":"8","author":"AP Porsteinsson","year":"2021","unstructured":"Porsteinsson AP, Isaacson R, Knox S, Sabbagh MN, Rubino I (2021) Diagnosis of early alzheimer\u2019s disease: clinical practice in 2021. J. Prevent Alzheimer\u2019s Dis. 8:371\u2013386","journal-title":"J. Prevent Alzheimer\u2019s Dis."},{"key":"4059_CR17","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.cma.2019.04.028","volume":"352","author":"A Sch\u00e4fer","year":"2019","unstructured":"Sch\u00e4fer A, Weickenmeier J, Kuhl E (2019) The interplay of biochemical and biomechanical degeneration in alzheimer\u2019s disease. Comput. Method Appl. Mech. Eng. 352:369\u2013388","journal-title":"Comput. Method Appl. Mech. Eng."},{"key":"4059_CR18","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.jmps.2018.10.013","volume":"124","author":"J Weickenmeier","year":"2019","unstructured":"Weickenmeier J, Jucker M, Goriely A, Kuhl E (2019) A physics-based model explains the prion-like features of neurodegeneration in alzheimer\u2019s disease, parkinson\u2019s disease, and amyotrophic lateral sclerosis. J. Mech. Phys. Solids 124:264\u2013281","journal-title":"J. Mech. Phys. Solids"},{"key":"4059_CR19","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1111\/j.1469-1809.1937.tb02153.x","volume":"7","author":"RA Fisher","year":"1937","unstructured":"Fisher RA (1937) The wave of advance of advantageous genes. Ann. Eugen. 7:355\u2013369","journal-title":"Ann. Eugen."},{"key":"4059_CR20","unstructured":"Kolmogorov, A., Petrovsky, I., Piskunov N., Investigation of the equation of diffusion combined with increasing of the substance and its application to a biology problem, Bull. Moscow State Univ. Ser. A: Math. Mech 1 (1937) 1\u201325."},{"key":"4059_CR21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008267","volume":"16","author":"TB Thompson","year":"2020","unstructured":"Thompson TB, Chaggar P, Kuhl E, Goriely A, Initiative ADN (2020) Protein-protein interactions in neurodegenerative diseases: a conspiracy theory. PLoS Computat. Biol. 16:e1008267","journal-title":"PLoS Computat. Biol."},{"key":"4059_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.brain.2024.100098","volume":"7","author":"M Corti","year":"2024","unstructured":"Corti M (2024) Exploring tau protein and amyloid-beta propagation: a sensitivity analysis of mathematical models based on biological data. Brain Multiphys. 7:100098","journal-title":"Brain Multiphys."},{"key":"4059_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.brain.2024.100103","volume":"7","author":"CA Stockman","year":"2024","unstructured":"Stockman CA, Goriely A, Kuhl E, Initiative ADN et al (2024) Two for tau: automated model discovery reveals two-stage tau aggregation dynamics in alzheimer\u2019s disease. Brain Multiphys. 7:100103","journal-title":"Brain Multiphys."},{"key":"4059_CR24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3003241","volume":"23","author":"P Chaggar","year":"2025","unstructured":"Chaggar P, Vogel JW, Binette AP, Thompson TB, Strandberg O, Mattsson-Carlgren N, Karlsson L, Stomrud E, Jbabdi S, Magon S et al (2025) Personalised regional modelling predicts tau progression in the human brain. PLoS Biol. 23:e3003241","journal-title":"PLoS Biol."},{"key":"4059_CR25","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s00285-024-02179-5","volume":"90","author":"GS Brennan","year":"2025","unstructured":"Brennan GS, Goriely A (2025) A network aggregation model for amyloid-$$\\beta$$ dynamics and treatment of alzheimer\u2019s diseases at the brain scale. J. Mathemat. Biol. 90:22","journal-title":"J. Mathemat. Biol."},{"key":"4059_CR26","doi-asserted-by":"crossref","unstructured":"Alexandersen C. G., Brennan G. S., Brynildsen J. K., Henderson M. X., Iturria-Medina Y., Bassett D. S., Network models of neurodegeneration: bridging neuronal dynamics and disease progression, IEEE Rev Biomed Eng (2026).","DOI":"10.1109\/RBME.2025.3643310"},{"key":"4059_CR27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0010042","volume":"1","author":"O Sporns","year":"2005","unstructured":"Sporns O, Tononi G, K\u00f6tter R (2005) The human connectome: a structural description of the human brain. PLoS Comput. Biol. 1:e42","journal-title":"PLoS Comput. Biol."},{"key":"4059_CR28","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/nrn2575","volume":"10","author":"E Bullmore","year":"2009","unstructured":"Bullmore E, Sporns O (2009) Complex brain networks: graph theoretical analysis of structural and functional systems. Nat. Rev. Neurosci. 10:186\u2013198","journal-title":"Nat. Rev. Neurosci."},{"key":"4059_CR29","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","volume":"31","author":"RS Desikan","year":"2006","unstructured":"Desikan, R. S., F. S\u00e9gonne, B. Fischl, B. T. Quinn, B. C. Dickerson, D. Blacker, R. L. Buckner, A. M. Dale, R. P. Maguire, B. T. Hyman, et al. An automated labeling system for subdividing the human cerebral cortex on mri scans into gyral based regions of interest. Neuroimage. 31:968\u2013980, 2006.","journal-title":"Neuroimage"},{"key":"4059_CR30","doi-asserted-by":"publisher","first-page":"11597","DOI":"10.1523\/JNEUROSCI.2180-11.2011","volume":"31","author":"MF Glasser","year":"2011","unstructured":"Glasser MF, Van Essen DC (2011) Mapping human cortical areas in vivo based on myelin content as revealed by t1-and t2-weighted mri. J. Neurosci. 31:11597\u201311616","journal-title":"J. Neurosci."},{"key":"4059_CR31","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.neuroimage.2019.02.039","volume":"194","author":"O Civier","year":"2019","unstructured":"Civier, O., R. E. Smith, C.-H. Yeh, A. Connelly, and F. Calamante. Is removal of weak connections necessary for graph-theoretical analysis of dense weighted structural connectomes from diffusion mri? NeuroImage. 194:68\u201381, 2019.","journal-title":"NeuroImage"},{"key":"4059_CR32","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.566876","volume":"14","author":"A Sch\u00e4fer","year":"2020","unstructured":"Sch\u00e4fer A, Mormino EC, Kuhl E (2020) Network diffusion modeling explains longitudinal tau pet data. Front. Neurosci. 14:566876","journal-title":"Front. Neurosci."},{"key":"4059_CR33","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.neuroimage.2015.06.092","volume":"119","author":"RE Smith","year":"2015","unstructured":"Smith, R. E., J.-D. Tournier, F. Calamante, and A. Connelly. Sift2: Enabling dense quantitative assessment of brain white matter connectivity using streamlines tractography. Neuroimage. 119:338\u2013351, 2015.","journal-title":"Neuroimage"},{"key":"4059_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116137","volume":"202","author":"J-D Tournier","year":"2019","unstructured":"Tournier, J.-D., R. Smith, D. Raffelt, R. Tabbara, T. Dhollander, M. Pietsch, D. Christiaens, B. Jeurissen, C.-H. Yeh, and A. Connelly. Mrtrix3: A fast, flexible and open software framework for medical image processing and visualisation. Neuroimage.202:116137, 2019.","journal-title":"Neuroimage"},{"key":"4059_CR35","doi-asserted-by":"publisher","first-page":"3939","DOI":"10.1007\/s00366-022-01700-y","volume":"38","author":"A Ca\u00e7oilo","year":"2022","unstructured":"Ca\u00e7oilo A, Rusinek H, Weickenmeier J (2022) 3d finite-element brain modeling of lateral ventricular wall loading to rationalize periventricular white matter hyperintensity locations. Eng. Comput. 38:3939\u20133955","journal-title":"Eng. Comput."},{"key":"4059_CR36","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/S1474-4422(04)00853-1","volume":"3","author":"A Nordberg","year":"2004","unstructured":"Nordberg A (2004) Pet imaging of amyloid in alzheimer\u2019s disease. Lancet Neurol. 3:519\u2013527","journal-title":"Lancet Neurol."},{"key":"4059_CR37","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1212\/WNL.58.12.1791","volume":"58","author":"DR Thal","year":"2002","unstructured":"Thal, D. R., U. Rub, M. Orantes, and H. Braak. Phases of a$$\\beta$$-deposition in the human brain and its relevance for the development of ad. Neurology. 58:1791\u20131800, 2002.","journal-title":"Neurology"},{"key":"4059_CR38","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/BF00308809","volume":"82","author":"H Braak","year":"1991","unstructured":"Braak H, Braak E (1991) Neuropathological stageing of alzheimer-related changes. Acta Neuropathol. 82:239\u2013259","journal-title":"Acta Neuropathol."},{"key":"4059_CR39","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.neuron.2016.01.028","volume":"89","author":"M Sch\u00f6ll","year":"2016","unstructured":"Sch\u00f6ll, M., S. N. Lockhart, D. R. Schonhaut, J. P. O\u2019Neil, M. Janabi, R. Ossenkoppele, S. L. Baker, J. W. Vogel, J. Faria, H. D. Schwimmer, et al. Pet imaging of tau deposition in the aging human brain. Neuron. 89:971\u2013982, 2016.","journal-title":"Neuron"},{"key":"4059_CR40","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/s41380-020-0721-9","volume":"26","author":"H Zetterberg","year":"2021","unstructured":"Zetterberg H, Bendlin BB (2021) Biomarkers for alzheimer\u2019s disease-preparing for a new era of disease-modifying therapies. Mol. Psych. 26:296\u2013308","journal-title":"Mol. Psych."},{"key":"4059_CR41","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1148\/radiol.2482070938","volume":"248","author":"JD Sluimer","year":"2008","unstructured":"Sluimer, J. D., W. M. van der Flier, G. B. Karas, N. C. Fox, P. Scheltens, F. Barkhof, and H. Vrenken. Whole-brain atrophy rate and cognitive decline: longitudinal mr study of memory clinic patients. Radiology. 248:590\u2013598, 2008.","journal-title":"Radiology"},{"key":"4059_CR42","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1016\/j.neurobiolaging.2009.05.013","volume":"32","author":"KB Walhovd","year":"2011","unstructured":"Walhovd KB, Westlye LT, Amlien I, Espeseth T, Reinvang I, Raz N, Agartz I, Salat DH, Greve DN, Fischl B et al (2011) Consistent neuroanatomical age-related volume differences across multiple samples. Neurobiol. Aging 32:916\u2013932","journal-title":"Neurobiol. Aging"},{"key":"4059_CR43","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.1212\/WNL.0b013e3181a82634","volume":"72","author":"I Driscoll","year":"2009","unstructured":"Driscoll, I., C. Davatzikos, Y. An, X. Wu, D. Shen, M. Kraut, and S. Resnick. Longitudinal pattern of regional brain volume change differentiates normal aging from mci. Neurology. 72:1906\u20131913, 2009.","journal-title":"Neurology"},{"key":"4059_CR44","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.actbio.2016.07.040","volume":"42","author":"J Weickenmeier","year":"2016","unstructured":"Weickenmeier J, de Rooij R, Budday S, Steinmann P, Ovaert TC, Kuhl E (2016) Brain stiffness increases with myelin content. Acta Biomaterialia 42:265\u2013272","journal-title":"Acta Biomaterialia"},{"key":"4059_CR45","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.jmbbm.2017.04.017","volume":"76","author":"J Weickenmeier","year":"2017","unstructured":"Weickenmeier J, de Rooij R, Budday S, Ovaert TC, Kuhl E (2017) The mechanical importance of myelination in the central nervous system. J. Mech. Behav. Biomed. Mater. 76:119\u2013124","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"4059_CR46","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.actbio.2023.08.033","volume":"170","author":"X Zhang","year":"2023","unstructured":"Zhang, X., and J. Weickenmeier. Brain stiffness follows cuprizone-induced variations in local myelin content. Acta Biomaterialia. 170:507\u2013518, 2023.","journal-title":"Acta Biomaterialia"},{"key":"4059_CR47","doi-asserted-by":"publisher","first-page":"11050","DOI":"10.1073\/pnas.200033797","volume":"97","author":"B Fischl","year":"2000","unstructured":"Fischl B, Dale AM (2000) Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proceed. Natl. Acad. Sci. 97:11050\u201311055","journal-title":"Proceed. Natl. Acad. Sci."},{"key":"4059_CR48","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1114\/1.202","volume":"27","author":"MS Sacks","year":"1999","unstructured":"Sacks MS, Vorp DA, Raghavan M, Federle MP, Webster MW (1999) In vivo three-dimensional surface geometry of abdominal aortic aneurysms. Ann. Biomed. Eng. 27:469\u2013479","journal-title":"Ann. Biomed. Eng."},{"key":"4059_CR49","first-page":"2612","volume":"11","author":"JW Vogel","year":"2020","unstructured":"Vogel JW, Young AL, Oxtoby NP, Smith R, Ossenkoppele R, Strandberg OT, La Joie R, Aksman LM, Grothe MJ, Iturria-Medina Y et al (2020) Spread of pathological tau proteins through communicating neurons in human Alzheimer\u2019s disease. Nat. Communicat. 11:2612","journal-title":"Nat. Communicat."},{"key":"4059_CR50","first-page":"1","volume":"2","author":"Z Ahmed","year":"2014","unstructured":"Ahmed Z, Cooper J, Murray TK, Garn K, McNaughton E, Clarke H, Parhizkar S, Ward MA, Cavallini A, Jackson S et al (2014) Tau seeding and spreading mechanisms in neurodegeneration. Acta Neuropathol. Communicat. 2:1\u201311","journal-title":"Acta Neuropathol. Communicat."},{"key":"4059_CR51","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/S1474-4422(12)70291-0","volume":"12","author":"CR Jack Jr","year":"2013","unstructured":"Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigand SD et al (2013) Tracking pathophysiological processes in Alzheimer\u2019s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 12:207\u2013216","journal-title":"Lancet Neurol."},{"key":"4059_CR52","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1016\/j.neuron.2013.12.003","volume":"80","author":"CR Jack","year":"2013","unstructured":"Jack, C. R., and D. M. Holtzman. Biomarker modeling of alzheimer\u2019s disease. Neuron. 80:1347\u20131358, 2013.","journal-title":"Neuron"},{"key":"4059_CR53","doi-asserted-by":"publisher","DOI":"10.1063\/5.0294034","volume":"10","author":"N Tueni","year":"2026","unstructured":"Tueni N, Griffiths E, Weickenmeier J, Rampp S, Budday S (2026) Region-dependent mechanical parameters in simulating cerebral atrophy. APL Bioeng. 10:016104","journal-title":"APL Bioeng."},{"key":"4059_CR54","doi-asserted-by":"publisher","first-page":"3998","DOI":"10.1038\/s41598-019-39809-8","volume":"9","author":"P Coup\u00e9","year":"2019","unstructured":"Coup\u00e9 P, Manj\u00f3n JV, Lanuza E, Catheline G (2019) Lifespan changes of the human brain in alzheimer\u2019s disease. Sci. Rep. 9:3998","journal-title":"Sci. Rep."},{"issue":"2","key":"4059_CR55","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s13205-022-03123-4","volume":"12","author":"YL Rao","year":"2022","unstructured":"Rao YL, Ganaraja B, Murlimanju BV, Joy T, Krishnamurthy A, Agrawal A (2022) Hippocampus and its involvement in Alzheimer\u2019s disease: a review. 3 Biotech. 12(2):55","journal-title":"3 Biotech."},{"key":"4059_CR56","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.pscychresns.2011.06.014","volume":"194","author":"SP Poulin","year":"2011","unstructured":"Poulin SP, Dautoff R, Morris JC, Barrett LF, Dickerson BC, Initiative ADN et al (2011) Amygdala atrophy is prominent in early alzheimer\u2019s disease and relates to symptom severity. Psych. Res. Neuroimag. 194:7\u201313","journal-title":"Psych. Res. Neuroimag."},{"issue":"1","key":"4059_CR57","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.neuroimage.2008.07.016","volume":"43","author":"K Im","year":"2008","unstructured":"Im K, Lee JM, Seo SW, Kim SH, Kim SI, Na DL (2008) Sulcal morphology changes and their relationship with cortical thickness and gyral white matter volume in mild cognitive impairment and Alzheimer\u2019s disease. Neuroimage 43(1):103\u2013113","journal-title":"Neuroimage"},{"key":"4059_CR58","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1007\/s00401-013-1151-4","volume":"126","author":"JB Toledo","year":"2013","unstructured":"Toledo JB, Xie SX, Trojanowski JQ, Shaw LM (2013) Longitudinal change in csf tau and a$$\\beta$$\u00a0biomarkers for up to 48 months in adni. Acta Neuropathol. 126:659\u2013670","journal-title":"Acta Neuropathol."},{"key":"4059_CR59","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1056\/NEJMoa1202753","volume":"367","author":"RJ Bateman","year":"2012","unstructured":"Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM et al (2012) Clinical and biomarker changes in dominantly inherited alzheimer\u2019s disease. New England J. Med. 367:795\u2013804","journal-title":"New England J. Med."},{"key":"4059_CR60","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1007\/s10654-017-0326-z","volume":"33","author":"AK Ower","year":"2018","unstructured":"Ower AK, Hadjichrysanthou C, Gras L, Goudsmit J, Anderson RM, de Wolf F, Initiative ADN (2018) Temporal association patterns and dynamics of amyloid-$$\\beta$$ and tau in alzheimer\u2019s disease. Europ. J. Epidemiol. 33:657\u2013666","journal-title":"Europ. J. Epidemiol."},{"key":"4059_CR61","doi-asserted-by":"publisher","first-page":"2879","DOI":"10.1007\/s00259-020-04773-3","volume":"47","author":"MS Baek","year":"2020","unstructured":"Baek MS, Cho H, Lee HS, Choi JY, Lee JH, Ryu YH, Lee MS, Lyoo CH (2020) Temporal trajectories of in vivo tau and amyloid-$$\\beta$$ accumulation in alzheimer\u2019s disease. Europ. J. Nuclear Med. Mol. Imaging 47:2879\u20132886","journal-title":"Europ. J. Nuclear Med. Mol. Imaging"},{"key":"4059_CR62","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/s13195-023-01304-8","volume":"15","author":"K Blanco","year":"2023","unstructured":"Blanco K, Salcidua S, Orellana P, Sauma-P\u00e9rez T, Le\u00f3n T, Steinmetz LCL, Iba\u00f1ez A, Duran-Aniotz C, de la Cruz R (2023) Systematic review: fluid biomarkers and machine learning methods to improve the diagnosis from mild cognitive impairment to alzheimer\u2019s disease. Alzheimer\u2019s Res. Therapy 15:176","journal-title":"Alzheimer\u2019s Res. Therapy"},{"key":"4059_CR63","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s13311-016-0481-z","volume":"14","author":"SE Counts","year":"2017","unstructured":"Counts, S. E., M. D. Ikonomovic, N. Mercado, I. E. Vega, and E. J. Mufson. Biomarkers for the early detection and progression of alzheimer\u2019s disease. Neurotherapeutics. 14:35\u201353, 2017.","journal-title":"Neurotherapeutics"},{"key":"4059_CR64","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/S1474-4422(13)70044-9","volume":"12","author":"VL Villemagne","year":"2013","unstructured":"Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P et al (2013) Amyloid $$\\beta$$ deposition, neurodegeneration, and cognitive decline in sporadic alzheimer\u2019s disease: a prospective cohort study. Lancet Neurol. 12:357\u2013367","journal-title":"Lancet Neurol."},{"key":"4059_CR65","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S1474-4422(18)30028-0","volume":"17","author":"BA Gordon","year":"2018","unstructured":"Gordon BA, Blazey TM, Su Y, Hari-Raj A, Dincer A, Flores S, Christensen J, McDade E, Wang G, Xiong C et al (2018) Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant alzheimer\u2019s disease: a longitudinal study. Lancet Neurol. 17:241\u2013250","journal-title":"Lancet Neurol."},{"key":"4059_CR66","doi-asserted-by":"crossref","unstructured":"Q. Liu, D. Yang, J. Zhang, Z. Wei, G. Wu, M. Chen, Analyzing the spatiotemporal interaction and propagation of atn biomarkers in alzheimer\u2019s disease using longitudinal neuroimaging data, in: 2021 IEEE 18th International Symposium on Biomedical Imaging (ISBI), IEEE, pp. 126\u2013129.","DOI":"10.1109\/ISBI48211.2021.9434021"},{"key":"4059_CR67","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.3233\/JAD-230027","volume":"95","author":"J Zhang","year":"2023","unstructured":"Zhang J, Liu Q, Zhang H, Dai M, Song Q, Yang D, Wu G, Chen M (2023) Uncovering the system vulnerability and criticality of human brain under dynamical neuropathological events in alzheimer\u2019s disease. J. Alzheimer\u2019s Dis. 95:1201\u20131219","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"4059_CR68","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2023.103371","volume":"38","author":"T Bachmann","year":"2023","unstructured":"Bachmann T, Schroeter ML, Chen K, Reiman EM, Weise CM (2023) Longitudinal changes in surface based brain morphometry measures in amnestic mild cognitive impairment and Alzheimer\u2019s disease. NeuroImage Clin. 38:103371","journal-title":"NeuroImage Clin."},{"key":"4059_CR69","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0306270","volume":"19","author":"Y Wang","year":"2024","unstructured":"Wang, Y., M. Li, D. Haughton, and L. E. Kazis. Transition of mild cognitive impairment to alzheimer\u2019s disease: Medications as modifiable risk factors. Plos one.19:e0306270, 2024.","journal-title":"Plos One"},{"key":"4059_CR70","doi-asserted-by":"publisher","first-page":"1433426","DOI":"10.3389\/fnagi.2024.1433426","volume":"16","author":"M Ly","year":"2024","unstructured":"Ly M, Yu G, Son SJ, Pascoal T, Karim HT (2024) A disease Neuroimaging Initiative, Longitudinal accelerated brain age in mild cognitive impairment and alzheimer\u2019s disease. Front. Aging Neurosci. 16:1433426","journal-title":"Front. Aging Neurosci."},{"key":"4059_CR71","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1016\/j.neuroimage.2004.03.040","volume":"22","author":"PM Thompson","year":"2004","unstructured":"Thompson, P. M., K. M. Hayashi, G. I. De Zubicaray, A. L. Janke, S. E. Rose, J. Semple, M. S. Hong, D. H. Herman, D. Gravano, D. M. Doddrell, et al. Mapping hippocampal and ventricular change in alzheimer disease. Neuroimage. 22:1754\u20131766, 2004.","journal-title":"Neuroimage"},{"key":"4059_CR72","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1097\/WAD.0b013e3182163b62","volume":"26","author":"LG Apostolova","year":"2012","unstructured":"Apostolova LG, Green AE, Babakchanian S, Hwang KS, Chou Y-Y, Toga AW, Thompson PM (2012) Hippocampal atrophy and ventricular enlargement in normal aging, mild cognitive impairment (mci), and alzheimer disease. Alzheimer Dis. Assoc. Dis. 26:17\u201327","journal-title":"Alzheimer Dis. Assoc. Dis."},{"key":"4059_CR73","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1016\/j.acra.2020.07.039","volume":"28","author":"J Chen","year":"2021","unstructured":"Chen J, Mikheev AV, Yu H, Gruen MD, Rusinek H, Ge Y, Initiative ADN et al (2021) Bilateral distance partition of periventricular and deep white matter hyperintensities: performance of the method in the aging brain. Acad. Radiol. 28:1699\u20131708","journal-title":"Acad. Radiol."},{"key":"4059_CR74","doi-asserted-by":"publisher","first-page":"323","DOI":"10.3233\/JAD-220846","volume":"92","author":"P Newton","year":"2023","unstructured":"Newton P, Tchounguen J, Pettigrew C, Lim C, Lin Z, Lu H, Moghekar A, Albert M, Soldan A, B. R. Team, Newton P, Tchounguen J, Pettigrew C, Lim C, Lin Z (2023) Regional white matter hyperintensities and alzheimer\u2019s disease biomarkers among older adults with normal cognition and mild cognitive impairment. J. Alzheimer\u2019s Dis. 92:323\u2013339","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"4059_CR75","doi-asserted-by":"publisher","first-page":"21956","DOI":"10.1038\/s41598-021-00610-1","volume":"11","author":"VL Visser","year":"2021","unstructured":"Visser VL, Rusinek H, Weickenmeier J (2021) Peak ependymal cell stretch overlaps with the onset locations of periventricular white matter lesions. Sci. Rep. 11:21956","journal-title":"Sci. Rep."},{"key":"4059_CR76","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1001\/archneur.1983.04050110029003","volume":"40","author":"DF Benson","year":"1983","unstructured":"Benson DF, Kuhl DE, Hawkins RA, Phelps ME, Cummings JL, Tsai S (1983) The fluorodeoxyglucose 18f scan in alzheimer\u2019s disease and multi-infarct dementia. Arch. Neurol. 40:711\u2013714","journal-title":"Arch. Neurol."},{"key":"4059_CR77","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1053\/j.semnuclmed.2021.01.002","volume":"51","author":"S Minoshima","year":"2021","unstructured":"Minoshima S, Mosci K, Cross D, Thientunyakit T (2021) Brain [f-18] fdg pet for clinical dementia workup: differential diagnosis of alzheimer\u2019s disease and other types of dementing disorders. Seminars Nuclear Med. 51:230\u2013240","journal-title":"Seminars Nuclear Med."},{"key":"4059_CR78","doi-asserted-by":"publisher","first-page":"fcac109","DOI":"10.1093\/braincomms\/fcac109","volume":"4","author":"V Planche","year":"2022","unstructured":"Planche V, Manjon JV, Mansencal B, Lanuza E, Tourdias T, Catheline G, Coup\u00e9 P (2022) Structural progression of alzheimer\u2019s disease over decades: the mri staging scheme. Brain Communicat. 4:fcac109","journal-title":"Brain Communicat."},{"key":"4059_CR79","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1097\/01.jnen.0000182983.87106.d1","volume":"64","author":"DJ Bonthius","year":"2005","unstructured":"Bonthius DJ, Solodkin A, Van Hoesen GW (2005) Pathology of the insular cortex in alzheimer disease depends on cortical architecture. J. Neuropathol. Experiment. Neurol. 64:910\u2013922","journal-title":"J. Neuropathol. Experiment. Neurol."},{"key":"4059_CR80","doi-asserted-by":"publisher","first-page":"2826","DOI":"10.1007\/s00330-009-1512-5","volume":"19","author":"JD Sluimer","year":"2009","unstructured":"Sluimer JD, van der Flier WM, Karas GB, van Schijndel R, Barnes J, Boyes RG, Cover KS, Olabarriaga SD, Fox NC, Scheltens P et al (2009) Accelerating regional atrophy rates in the progression from normal aging to alzheimer\u2019s disease. Europ. Radiol. 19:2826\u20132833","journal-title":"Europ. Radiol."},{"key":"4059_CR81","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.3390\/brainsci11091232","volume":"11","author":"J Hwang","year":"2021","unstructured":"Hwang J, Kim CM, Kim JE, Oh M, Oh JS, Yoon YW, Kim JS, Lee J-H, Roh JH (2021) Clinical implications of amyloid-beta accumulation in occipital lobes in alzheimer\u2019s continuum. Brain Sci. 11:1232","journal-title":"Brain Sci."},{"key":"4059_CR82","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1093\/brain\/awm016","volume":"130","author":"A-T Du","year":"2007","unstructured":"Du, A.-T., N. Schuff, J. H. Kramer, H. J. Rosen, M. L. Gorno-Tempini, K. Rankin, B. L. Miller, and M. W. Weiner. Different regional patterns of cortical thinning in alzheimer\u2019s disease and frontotemporal dementia. Brain. 130:1159\u20131166, 2007.","journal-title":"Brain"},{"key":"4059_CR83","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1016\/j.neuropsychologia.2007.10.026","volume":"46","author":"LG Apostolova","year":"2008","unstructured":"Apostolova, L. G., and P. M. Thompson. Mapping progressive brain structural changes in early alzheimer\u2019s disease and mild cognitive impairment. Neuropsychologia. 46:1597\u20131612, 2008.","journal-title":"Neuropsychologia"},{"key":"4059_CR84","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1038\/s41398-021-01599-x","volume":"11","author":"B-S Wu","year":"2021","unstructured":"Wu B-S, Zhang Y-R, Li H-Q, Kuo K, Chen S-D, Dong Q, Liu Y, Yu J-T (2021) Cortical structure and the risk for alzheimer\u2019 s disease: a bidirectional mendelian randomization study. Translat. Psych. 11:476","journal-title":"Translat. Psych."},{"key":"4059_CR85","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.593898","volume":"13","author":"Z Wu","year":"2021","unstructured":"Wu Z, Peng Y, Hong M, Zhang Y (2021) Gray matter deterioration pattern during alzheimer\u2019s disease progression: a regions-of-interest based surface morphometry study. Front. Aging Neurosci. 13:593898","journal-title":"Front. Aging Neurosci."},{"key":"4059_CR86","doi-asserted-by":"publisher","first-page":"1214083","DOI":"10.3389\/fneur.2023.1214083","volume":"14","author":"MM Coleman","year":"2023","unstructured":"Coleman MM, Keith CM, Wilhelmsen K, Mehta RI, Vieira Ligo Teixeira C, Miller M, Ward M, Navia RO, McCuddy WT et al (2023) Surface-based correlates of cognition along the alzheimer\u2019s continuum in a memory clinic population. Front. Neurol. 14:1214083","journal-title":"Front. Neurol."},{"key":"4059_CR87","doi-asserted-by":"publisher","first-page":"e1714232024","DOI":"10.1523\/JNEUROSCI.1714-23.2024","volume":"44","author":"SA Maboudian","year":"2024","unstructured":"Maboudian SA, Willbrand EH, Kelly JP, Jagust WJ, Weiner KS, Initiative ADN et al (2024) Defining overlooked structures reveals new associations between the cortex and cognition in aging and alzheimer\u2019s disease. J. Neurosci. 44:e1714232024","journal-title":"J. Neurosci."}],"container-title":["Annals of Biomedical Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10439-026-04059-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10439-026-04059-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10439-026-04059-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:02:28Z","timestamp":1791486148000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10439-026-04059-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,24]]},"references-count":87,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["4059"],"URL":"https:\/\/doi.org\/10.1007\/s10439-026-04059-z","relation":{},"ISSN":["0090-6964","1573-9686"],"issn-type":[{"value":"0090-6964","type":"print"},{"value":"1573-9686","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,24]]},"assertion":[{"value":"6 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Ethical Approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent to Participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":4,"name":"Ethics","label":"Consent for Publication","group":{"name":"EthicsHeading","label":"Declarations"}}]}}