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While considered relatively non-toxic at low concentrations, DMSO itself may exert biological effects that could confound experimental outcomes, especially for weakly cytotoxic substances like A\u03b2. Seven brain cell types (BV-2, N2a, SH-SY5Y, U87, neurons, astrocytes, microglia) were treated with varying DMSO concentrations or A\u03b21-42 oligomers\/protofibrils\/fibrils prepared using DMSO. Cell viability was assessed by CCK-8 and LDH assays. Matched DMSO controls were prepared alongside A\u03b2 treatments to delineate solvent effects. Low DMSO concentrations (0.0625-0.015625%) exhibited hormetic cytoprotective and growth-promoting effects, while higher concentrations (\u22652%) were cytotoxic. Importantly, these hormetic solvent effects confounded the measurement of A\u03b2 cytotoxicity. By accounting for matched DMSO controls, the study revealed that A\u03b2 fibril toxicity may have been underestimated due to the cytoprotective solvent effects of low DMSO concentrations used in their preparation. In conclusion, DMSO exhibits complex hormetic dose-responses that can significantly influence experimental outcomes, especially for weakly cytotoxic agents like A\u03b2. Rigorous solvent controls are crucial to delineate genuine substance effects from potential solvent confounds and avoid erroneous interpretations.<\/jats:p>","DOI":"10.1177\/10915818251338235","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T15:12:32Z","timestamp":1747321952000},"page":"297-313","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of Solvent Dimethyl Sulfoxide Invites a Rethink of Its Application in Amyloid Beta Cytotoxicity"],"prefix":"10.1177","volume":"44","author":[{"given":"Yanhong","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Neurology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China"},{"name":"Center for Cognition and Sleep, The People\u2019s Hospital of Guangxi Zhuang Autonomous Region &amp; Institute of Brain and Mental Diseases, Guangxi Academy of Medical Sciences, Nanning, 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