{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:11:31Z","timestamp":1787022691011,"version":"build-2736575974"},"reference-count":85,"publisher":"Society for Neuroscience","issue":"4","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Universities","award":["FPU2019-04251"],"award-info":[{"award-number":["FPU2019-04251"]}]},{"name":"European Union eBRAIN-Health consortium","award":["HORIZON-101058516"],"award-info":[{"award-number":["HORIZON-101058516"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["eNeuro"],"accepted":{"date-parts":[[2023,12,22]]},"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:p>\n                    The accumulation of amyloid-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (\n                    <jats:italic>A\u03b2<\/jats:italic>\n                    ) and hyperphosphorylated-tau (hp-tau) are two classical histopathological biomarkers in Alzheimer\u2019s disease (AD). However, their detailed interactions with the electrophysiological changes at the meso- and macroscale are not yet fully understood. We developed a mechanistic multiscale model of AD progression, linking proteinopathy to its effects on neural activity and vice-versa. We integrated a heterodimer model of prion-like protein propagation and a brain network model of Jansen\u2013Rit neural masses derived from human neuroimaging data whose parameters varied due to neurotoxicity. Results showed that changes in inhibition guided the electrophysiological alterations found in AD, and these changes were mainly attributed to\n                    <jats:italic>A\u03b2<\/jats:italic>\n                    effects. Additionally, we found a causal disconnection between cellular hyperactivity and interregional hypersynchrony contrary to previous beliefs. Finally, we demonstrated that early\n                    <jats:italic>A\u03b2<\/jats:italic>\n                    and hp-tau depositions\u2019 location determine the spatiotemporal profile of the proteinopathy. The presented model combines the molecular effects of both\n                    <jats:italic>A\u03b2<\/jats:italic>\n                    and hp-tau together with a mechanistic protein propagation model and network effects within a closed-loop model. This holds the potential to enlighten the interplay between AD mechanisms on various scales, aiming to develop and test novel hypotheses on the contribution of different AD-related variables to the disease evolution.\n                  <\/jats:p>","DOI":"10.1523\/eneuro.0345-23.2023","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T13:50:23Z","timestamp":1712065823000},"page":"ENEURO.0345-23.2023","source":"Crossref","is-referenced-by-count":13,"title":["A Multiscale Closed-Loop Neurotoxicity Model of Alzheimer\u2019s Disease Progression Explains Functional Connectivity 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