{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:39:45Z","timestamp":1783125585927,"version":"3.54.6"},"reference-count":74,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2023,9,26]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Despite the striking efforts in investigating neurobiological factors behind the acquisition of amyloid-\u03b2 (A), protein tau (T), and neurodegeneration ([N]) biomarkers, the mechanistic pathways of how AT[N] biomarkers spreading throughout the brain remain elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To disentangle the massive heterogeneities in Alzheimer\u2019s disease (AD) progressions and identify vulnerable\/critical brain regions to AD pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In this work, we characterized the interaction of AT[N] biomarkers and their propagation across brain networks using a novel bistable reaction-diffusion model, which allows us to establish a new systems biology underpinning of AD progression. We applied our model to large-scale longitudinal neuroimages from the ADNI database and studied the systematic vulnerability and criticality of brains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Our model yields long term prediction that is statistically significant linear correlated with temporal imaging data, produces clinically consistent risk prediction, and captures the Braak-like spreading pattern of AT[N] biomarkers in AD development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our major findings include (i) tau is a stronger indicator of regional risk compared to amyloid, (ii) temporal lobe exhibits higher vulnerability to AD-related pathologies, (iii) proposed critical brain regions outperform hub nodes in transmitting disease factors across the brain, and (iv) comparing the spread of neuropathological burdens caused by amyloid-\u03b2 and tau diffusions, disruption of metabolic balance is the most determinant factor contributing to the initiation and progression of AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-230027","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T11:26:33Z","timestamp":1693567593000},"page":"1201-1219","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Uncovering the System Vulnerability and Criticality of Human Brain Under Dynamical Neuropathological Events in Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"95","author":[{"given":"Jingwen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Computer Science, Wake Forest University, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of North Georgia, Oakwood, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haorui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of North Georgia, Oakwood, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. 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