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. 2021 Aug 12;16:55. doi: 10.1186/s13024-021-00474-z

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — Major historical events in mass spectrometry and AD research. Edman degradation is also included. The AD proteomics studies are highlighted. The information is compiled from several online resources (https://www.nature.com/collections/aajfehieag, https://www.hupo.org/Proteomics-Timeline, https://masspec.scripps.edu/learn/ms, https://www.alzforum.org/timeline, and https://www.alzheimers.net/history-of-alzheimers) and references [74, 75, 79, 80, 82, 96–102]. MS detection instruments include sector MS, time-of-flight (TOF), quadrupole, Fourier-transform ion cyclotron resonance (FTICR), triple quadrupole, and orbitrap. Common ionization methods include atmospheric pressure chemical ionization (APCI), electrospray ionization (ESI), matrix-assisted laser desorption/ionization (MALDI), desorption electrospray ionization (DESI), and direct analysis in real time (DART). Biomolecules may be fractionated by nanoscale liquid chromatography (LC) with sub-2 μm resin to improve resolution, or by multi-dimensional protein identification technology (MudPIT). MS precursor ions can be fragmented by collision-induced dissociation (CID), electron-capture dissociation (ECD), electron-transfer dissociation (ETD), or higher-energy collisional dissociation (HCD). Quantitative strategies include two dimensional polyacryl amide gel electrophoresis (2D PAGE), isotope-coded affinity tag (ICAT), stable isotope labeling by/with amino acids in cell culture (SILAC), tandem mass tag (TMT), isobaric tags for relative and absolute quantitation (iTRAQ), and the data-independent acquisition (DIA) methods. Selected/multiple reaction monitoring (SRM/MRM) is a MS technique for analyzing pre-defined molecules. Database search tools contain SEQUEST, MASCOT, and the target-decoy strategy. CAA: cerebral amyloid angiopathy; LCM: laser capture microdissection; GWAS: genome-wide association study; CSF: cerebrospinal fluid; and FDA: the United States Food and Drug Administration