{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:15:50Z","timestamp":1786976150980,"version":"build-2736575974"},"reference-count":62,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:00:00Z","timestamp":1579651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007464","name":"Torsten S\u00f6derbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007464","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:p>\n                    Alzheimer's disease (AD) is the most common form of dementia, affecting millions of people and currently lacking available disease\u2010modifying treatments. Appropriate disease models are necessary to investigate disease mechanisms and potential treatments.\n                    <jats:italic>Drosophila\u00a0melanogaster<\/jats:italic>\n                    models of AD include the A\u03b2 fly model and the A\u03b2PP\u2010BACE1 fly model. In the A\u03b2 fly model, the A\u03b2 peptide is fused to a secretion sequence and directly overexpressed. In the A\u03b2PP\u2010BACE1 model, human A\u03b2PP and human BACE1 are expressed in the fly, resulting in\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    production of A\u03b2 peptides and other A\u03b2PP cleavage products. Although these two models have been used for almost two decades, the underlying mechanisms resulting in neurodegeneration are not yet clearly understood. In this study, we have characterized toxic mechanisms in these two AD fly models. We detected neuronal cell death and increased protein carbonylation (indicative of oxidative stress) in both AD fly models. In the A\u03b2 fly model, this correlates with high A\u03b2\n                    <jats:sub>1\u201342<\/jats:sub>\n                    levels and down\u2010regulation of the levels of mRNA encoding lysosomal\u2010associated membrane protein 1,\n                    <jats:italic>lamp1<\/jats:italic>\n                    (a lysosomal marker), while in the A\u03b2PP\u2010BACE1 fly model, neuronal cell death correlates with low A\u03b2\n                    <jats:sub>1\u201342<\/jats:sub>\n                    levels, up\u2010regulation of\n                    <jats:italic>lamp1<\/jats:italic>\n                    mRNA levels and increased levels of C\u2010terminal fragments. In addition, a significant amount of A\u03b2PP\/A\u03b2 antibody (4G8)\u2010positive species, located close to the endosomal marker rab5, was detected in the A\u03b2PP\u2010BACE1 model. Taken together, this study highlights the similarities and differences in the toxic mechanisms which result in neuronal death in two different AD fly models. Such information is important to consider when utilizing these models to study AD pathogenesis or screening for potential treatments.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.12773","type":"journal-article","created":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T03:20:26Z","timestamp":1576034426000},"page":"338-350","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Mapping pathogenic processes contributing to neurodegeneration in\n                    <i>Drosophila<\/i>\n                    models of Alzheimer's disease"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7433-2647","authenticated-orcid":false,"given":"Liza","family":"Bergkvist","sequence":"first","affiliation":[{"name":"Division of Molecular Biotechnology Department of Physics, Chemistry and Biology Link\u00f6ping University 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