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, 96,97,98,99,100,101,102]. 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