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This study provides a systematic framework for analyzing A\u03b2(1\u201342) oligomers in vitro using cyclic ion mobility-mass spectrometry (cIMS). Compared to previous generations of traveling wave ion mobility (TWIM) devices, the cIMS platform offers superior resolution through its scalable ion mobility path length. However, the multistage character of the cIMS platform requires thorough investigation of parameters affecting oligomer transmission and activation to ensure reliable analysis of labile and dynamic systems such as A\u03b2 oligomers. Our findings highlight the critical influence of cone voltage (CV) on in-source ion activation, subsequent structural changes, and oligomer detection. By balancing CV, we achieved detection of a broad range of oligomeric species while limiting their activation and maximizing signal intensity. Moreover, we present the first comprehensive set of optimized ion optics and ion mobility parameters that enable effective transmission and separation of oligomer A\u03b2(1\u201342) ions. Using the optimized method, we successfully detected a spectrum of A\u03b2(1\u201342) oligomers ranging from dimers to dodecamers. Additionally, the method was applied in collision-induced unfolding experiments, revealing size-dependent conformational transitions proving its applicability. This optimized cIMS methodology establishes a foundation for future studies on A\u03b2(1\u201342) aggregation mechanisms, AD pathogenesis, and therapeutic applications. Furthermore, our results offer valuable insights into cIMS instrument tuning, with potential applications in the analysis of other complex biological systems.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s00216-026-06349-w","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T07:44:35Z","timestamp":1769845475000},"page":"2273-2286","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Analysis of amyloid beta oligomers by cyclic ion mobility-mass spectrometry"],"prefix":"10.1007","volume":"418","author":[{"given":"Mikul\u00e1\u0161","family":"Vlk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Muck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Hey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean F.","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hub\u00e1lek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3590-9009","authenticated-orcid":false,"given":"Josef","family":"Cva\u010dka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"6349_CR1","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/S0140-6736(15)01124-1","volume":"388","author":"P Scheltens","year":"2016","unstructured":"Scheltens P, Blennow K, Breteler MMB, de Strooper B, Frisoni GB, Salloway S, Van der Flier WM. 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