{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T12:42:13Z","timestamp":1733316133454,"version":"3.30.1"},"update-to":[{"updated":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"DOI":"10.1371\/journal.pcbi.1009114","type":"new_version","label":"New version"}],"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"Oligomers of the amyloid \u03b2<\/jats:italic>-protein (A\u03b2<\/jats:italic>) have been implicated in the pathogenesis of Alzheimer\u2019s disease (AD) through their toxicity towards neurons. Understanding the process of oligomerization may contribute to the development of therapeutic agents, but this has been difficult due to the complexity of oligomerization and the metastability of the oligomers thus formed. To understand the kinetics of oligomer formation, and how that relates to the progression of AD, we developed models of the oligomerization process. Here, we use experimental data from cell viability assays and proxies for rate constants involved in monomer-dimer-trimer kinetics to develop a simple mathematical model linking A\u03b2<\/jats:italic> assembly to oligomer-induced neuronal degeneration. This model recapitulates the rapid growth of disease incidence with age. It does so through incorporation of age-dependent changes in rates of A\u03b2<\/jats:italic> monomer production and elimination. The model also describes clinical progression in genetic forms of AD (e.g., Down\u2019s syndrome), changes in hippocampal volume, AD risk after traumatic brain injury, and spatial spreading of the disease due to foci in which A\u03b2<\/jats:italic> production is elevated. Continued incorporation of clinical and basic science data into the current model will make it an increasingly relevant model system for doing theoretical calculations that are not feasible in biological systems. In addition, terms in the model that have particularly large effects are likely to be especially useful therapeutic targets.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009114","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T17:37:42Z","timestamp":1626716262000},"page":"e1009114","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["From reaction kinetics to dementia: A simple dimer model of Alzheimer\u2019s disease etiology"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2841-1691","authenticated-orcid":true,"given":"Michael R.","family":"Lindstrom","sequence":"first","affiliation":[]},{"given":"Manuel B.","family":"Chavez","sequence":"additional","affiliation":[]},{"given":"Elijah 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