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These plaques are formed by aggregation of polypeptides that are derived from the Amyloid Precursor Protein (APP). Amyloid-\u03b2 plaques are thought to play either a direct or an indirect role in disease progression, however the exact role of aggregation and plaque formation in the aetiology of Alzheimer\u2019s disease (AD) is subject to debate as the biological effects of soluble and aggregated Amyloid-\u03b2 peptides are difficult to separate in vivo. To investigate the consequences of formation of Amyloid-\u03b2 oligomers in living tissues, we developed a fluorescently tagged, optogenetic Amyloid-\u03b2 peptide that oligomerizes rapidly in the presence of blue light. We applied this system to the crucial question of how intracellular Amyloid-\u03b2 oligomers underlie the pathologies of A. We use Drosophila, C. elegans and D. rerio to show that, although both expression and induced oligomerization of Amyloid-\u03b2 were detrimental to lifespan and healthspan, we were able to separate the metabolic and physical damage caused by light-induced Amyloid-\u03b2 oligomerization from Amyloid-\u03b2 expression alone. The physical damage caused by Amyloid-\u03b2 oligomers also recapitulated the catastrophic tissue loss that is a hallmark of late AD. We show that the lifespan deficit induced by Amyloid-\u03b2 oligomers was reduced with Li+ treatment. Our results present the first model to separate different aspects of disease progression.<\/jats:p>","DOI":"10.7554\/elife.52589","type":"journal-article","created":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T20:00:19Z","timestamp":1585598419000},"source":"Crossref","is-referenced-by-count":42,"title":["Application of optogenetic Amyloid-\u03b2 distinguishes between metabolic and physical damages in neurodegeneration"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6691-8277","authenticated-orcid":true,"given":"Chu Hsien","family":"Lim","sequence":"first","affiliation":[{"name":"Science Division, Yale- NUS College, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prameet","family":"Kaur","sequence":"additional","affiliation":[{"name":"Science Division, Yale- NUS College, Singapore, 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