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Biol."],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzheimer\u2019s disease (AD) is a common neurodegenerative disorder nowadays. Amyloid\u2010beta (A\u03b2) and tau proteins are among the main contributors to the AD progression. In AD, A\u03b2 proteins clump together to form plaques and disrupt cell functions. On the other hand, the abnormal chemical change in the brain helps to build sticky tau tangles that block the neuron\u2019s transport system. Astrocytes generally maintain a healthy balance in the brain by clearing the A\u03b2 plaques (toxic A\u03b2). However, overactivated astrocytes release chemokines and cytokines in the presence of A\u03b2 and react to pro\u2010inflammatory cytokines, further increasing the production of A\u03b2. In this study, we construct a mathematical model that can capture astrocytes\u2019 dual behavior. Furthermore, we reveal that the disease progression depends on the current time instance and the disease\u2019s earlier status, called the \u201cmemory effect,\u201d making non\u2010Markovian processes an appropriate approach. We consider a fractional order network mathematical model to capture the influence of such memory effects on AD progression. We have integrated brain connectome data into the model and studied the memory effect, the dual role of astrocytes, and the brain\u2019s neuronal damage. Based on the pathology, primary, secondary, and mixed tauopathies parameters are considered in the model. Due to the mixed tauopathy, different brain nodes or regions in the brain connectome accumulate different toxic concentrations of A\u03b2 and tau proteins. Finally, we explain how the memory effect can slow down the propagation of such toxic proteins in the brain, decreasing the rate of neuronal damage.<\/jats:p>","DOI":"10.1002\/qub2.70001","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T08:50:16Z","timestamp":1744620616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Complex non\u2010Markovian dynamics and the dual role of astrocytes in Alzheimer\u2019s disease development and propagation"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6873-7338","authenticated-orcid":false,"given":"Swadesh","family":"Pal","sequence":"first","affiliation":[{"name":"MS2 Discovery Interdisciplinary Research Institute Wilfrid Laurier University  Waterloo ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick","family":"Melnik","sequence":"additional","affiliation":[{"name":"MS2 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