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Advances in sample preparation and HPLC–MS/MS methods for determining amyloid-β peptide in biological samples: a review

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Abstract

Alzheimer’s disease (AD), a neurological disorder, is a major public health concern and the most common form of dementia. Its typical symptoms include memory loss, confusion, changes in personality, and cognitive impairment, which result in patients gradually losing independence. Over the last decades, some studies have focused on searching for effective biomarkers as early diagnostic indicators of AD. Amyloid-β (Aβ) peptides have been consolidated as reliable AD biomarkers and have been incorporated into modern diagnostic research criteria. However, quantitative analysis of Aβ peptides in biological samples remains a challenge because both the sample and the physical–chemical properties of these peptides are complex. During clinical routine, Aβ peptides are measured in the cerebrospinal fluid by immunoassays, but the availability of a specific antibody is critical—in some cases, an antibody may not exist, or its specificity may be inadequate, leading to low sensitivity and false results. HPLC-MS/MS has been reported as a sensitive and selective method for determining different fragments of Aβ peptides in biological samples simultaneously. Developments in sample preparation techniques (preconcentration platforms) such as immunoprecipitation, 96-well plate SPME, online SPME, and fiber-in-tube SPME have enabled not only effective enrichment of Aβ peptides present at trace levels in biological samples, but also efficient exclusion of interferents from the sample matrix (sample cleanup). This high extraction efficiency has provided MS platforms with higher sensitivity. Recently, methods affording LLOQ values as low as 5 pg mL−1 have been reported. Such low LLOQ values are adequate for quantifying Aβ peptides in complex matrixes including cerebrospinal fluid (CSF) and plasma samples. This review summarizes the advances in mass spectrometry (MS)-based methods for quantifying Aβ peptides and covers the period 1992–2022. Important considerations regarding the development of the HPLC-MS/MS method such as the sample preparation step, optimization of the HPLC-MS/MS parameters, and matrix effects are described. Clinical applications, difficulties related to analysis of plasma samples, and future trends of these MS/MS-based methods are also discussed.

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References

  1. Henry MS, Passmore AP, Todd S, McGuinness B, Craig D, Johnston JA. The development of effective biomarkers for Alzheimer’s disease: a review. Int J Geriatr Psychiatry. 2013;28:331–40. https://doi.org/10.1002/gps.3829.

    Article  PubMed  Google Scholar 

  2. Lee JC, Kim SJ, Hong S, Kim Y. Diagnosis of Alzheimer’s disease utilizing amyloid and tau as fluid biomarkers. Exp Mol Med. 2019;51:1–10. https://doi.org/10.1038/s12276-019-0250-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Glenner GG, Wong CW. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984;120:885–90. https://doi.org/10.1016/S0006-291X(84)80190-4.

    Article  CAS  PubMed  Google Scholar 

  4. Guzman-Martinez L, Maccioni RB, Farías GA, Fuentes P, Navarrete LP. Biomarkers for Alzheimer’s disease. Curr Alzheimer Res. 2019;16:518–28. https://doi.org/10.2174/1567205016666190517121140.

    Article  CAS  PubMed  Google Scholar 

  5. Chong JR, Ashton NJ, Karikari TK, Tanaka T, Schöll M, Zetterberg H, Blennow K, Chen CP, Lai MKP. Blood-based high sensitivity measurements of beta-amyloid and phosphorylated tau as biomarkers of Alzheimer’s disease: a focused review on recent advances. J Neurol Neurosurg Psychiatry. 2021;92:1231–41. https://doi.org/10.1136/jnnp-2021-327370.

    Article  PubMed  Google Scholar 

  6. Souza ID, Anderson JL, Queiroz MEC. Crosslinked zwitterionic polymeric ionic liquid-functionalized nitinol wires for fiber-in-tube solid-phase microextraction and UHPLC-MS/MS as an amyloid beta peptide binding protein assay in biological fluids. Anal Chim Acta. 2022; 1193:339394. https://doi.org/10.1016/j.aca.2021.339394.

  7. Bros P, Delatour V, Vialaret J, Lalere B, Barthelemy N, Gabelle A, Lehmann S, Hirtz C. Quantitative detection of amyloid-β peptides by mass spectrometry: state of the art and clinical applications. Clin Chem Lab Med. 2015;53. https://doi.org/10.1515/cclm-2014-1048.

  8. Zakharova NV, Bugrova AE, Kononikhin AS, Indeykina MI, Popov IA, Nikolaev EN. Mass spectrometry analysis of the diversity of Aβ peptides: difficulties and future perspectives for AD biomarker discovery. Exp Rev Proteomics. 2018;15:773–5. https://doi.org/10.1080/14789450.2018.1525296.

    Article  CAS  Google Scholar 

  9. Molinuevo JL, Ayton S, Batrla R, Bednar MM, Bittner T, Cummings J, Fagan AM, Hampel H, Mielke MM, Mikulskis A, O’Bryant S, Scheltens P, Sevigny J, Shaw LM, Soares HD, Tong G, Trojanowski JQ, Zetterberg H, Blennow K. Current state of Alzheimer’s fluid biomarkers. Acta Neuropathol. 2018;136:821–53. https://doi.org/10.1007/s00401-018-1932-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Saido T, Leissring MA. Proteolytic degradation of amyloid-protein. Cold Spring Harb Perspect Med. 2012;2:a006379–a006379. https://doi.org/10.1101/cshperspect.a006379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y. Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: evidence that an initially deposited species is Aβ42(43). Neuron. 1994;13:45–53. https://doi.org/10.1016/0896-6273(94)90458-8.

    Article  CAS  PubMed  Google Scholar 

  12. Lista S, Garaci FG, Ewers M, Teipel S, Zetterberg H, Blennow K, Hampel H. CSF Aβ1-42 combined with neuroimaging biomarkers in the early detection, diagnosis and prediction of Alzheimer’s disease. Alzheimer’s Dement. 2014;10:381–92. https://doi.org/10.1016/j.jalz.2013.04.506.

    Article  Google Scholar 

  13. Genin E, Hannequin D, Wallon D, Sleegers K, Hiltunen M, Combarros O, Bullido MJ, Engelborghs S, De Deyn P, Berr C, Pasquier F, Dubois B, Tognoni G, Fiévet N, Brouwers N, Bettens K, Arosio B, Coto E, Del Zompo M, Mateo I, Epelbaum J, Frank-Garcia A, Helisalmi S, Porcellini E, Pilotto A, Forti P, Ferri R, Scarpini E, Siciliano G, Solfrizzi V, Sorbi S, Spalletta G, Valdivieso F, Vepsäläinen S, Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B, Bossù P, Hanon O, Piccardi P, Annoni G, Seripa D, Galimberti D, Licastro F, Soininen H, Dartigues J-F, Kamboh MI, Van Broeckhoven C, Lambert JC, Amouyel P, Campion D. APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Mol Psychiatry. 2011;16:903–7. https://doi.org/10.1038/mp.2011.52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Soria Lopez JA, González HM, Léger GC. Alzheimer’s disease. Handb Clin Neurol. 2019;167:231–55. https://doi.org/10.1016/B978-0-12-804766-8.00013-3.

    Article  PubMed  Google Scholar 

  15. de Calignon A, Fox LM, Pitstick R, Carlson GA, Bacskai BJ, Spires-Jones TL, Hyman BT. Caspase activation precedes and leads to tangles. Nature. 2010;464:1201–4. https://doi.org/10.1038/nature08890.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Basurto-Islas G, Luna-Muñoz J, Guillozet-Bongaarts AL, Binder LI, Mena R, García-Sierra F. Accumulation of aspartic acid 421 - and glutamic acid 391 - cleaved tau in neurofibrillary tangles correlates with progression in Alzheimer disease. J Neuropathol Exp Neurol. 2008;67:470–83. https://doi.org/10.1097/NEN.0b013e31817275c7.

    Article  CAS  PubMed  Google Scholar 

  17. Alonso A del C, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K. Hyperphosphorylation induces self-assembly of τ into tangles of paired helical filaments/straight filaments. Proc Natl Acad Sci. 2001;98:6923–6928. https://doi.org/10.1073/pnas.121119298.

  18. James BD, Wilson RS, Boyle PA, Trojanowski JQ, Bennett DA, Schneider JA. TDP-43 stage, mixed pathologies, and clinical Alzheimer’s-type dementia. Brain. 2016;139:2983–93. https://doi.org/10.1093/brain/aww224.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kovacs GG, Milenkovic I, Wöhrer A, Höftberger R, Gelpi E, Haberler C, Hönigschnabl S, Reiner-Concin A, Heinzl H, Jungwirth S, Krampla W, Fischer P, Budka H. Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series. Acta Neuropathol. 2013;126:365–84. https://doi.org/10.1007/s00401-013-1157-y.

    Article  CAS  PubMed  Google Scholar 

  20. Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R, Elliott C, Masliah E, Ryan L, Silverberg N. NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimer’s Dement. 2018;14:535–62. https://doi.org/10.1016/j.jalz.2018.02.018.

    Article  Google Scholar 

  21. Hansson O, Lehmann S, Otto M, Zetterberg H, Lewczuk P. Advantages and disadvantages of the use of the CSF amyloid β (Aβ) 42/40 ratio in the diagnosis of Alzheimer’s disease. Alzheimers Res Ther. 2019;11:34. https://doi.org/10.1186/s13195-019-0485-0.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Janelidze S, Zetterberg H, Mattsson N, Palmqvist S, Vanderstichele H, Lindberg O, Westen D, Stomrud E, Minthon L, Blennow K, Hansson O. CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: better diagnostic markers of Alzheimer disease. Ann Clin Transl Neurol. 2016;3:154–65. https://doi.org/10.1002/acn3.274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ovod V, Ramsey KN, Mawuenyega KG, Bollinger JG, Hicks T, Schneider T, Sullivan M, Paumier K, Holtzman DM, Morris JC, Benzinger T, Fagan AM, Patterson BW, Bateman RJ. Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimer’s Dement. 2017;13:841–9. https://doi.org/10.1016/j.jalz.2017.06.2266.

    Article  Google Scholar 

  24. Korecka M, Waligorska T, Figurski M, Toledo JB, Arnold SE, Grossman M, Trojanowski JQ, Shaw LM. Qualification of a surrogate matrix-based absolute quantification method for amyloid-β42 in Human cerebrospinal fluid using 2D UPLC-tandem mass spectrometry. J Alzheimer’s Dis. 2014;41:441–51. https://doi.org/10.3233/JAD-132489.

    Article  CAS  Google Scholar 

  25. Leinenbach A, Pannee J, Dülffer T, Huber A, Bittner T, Andreasson U, Gobom J, Zetterberg H, Kobold U, Portelius E, Blennow K. Mass spectrometry–based candidate reference measurement procedure for quantification of amyloid-β in cerebrospinal fluid. Clin Chem. 2014;60:987–94. https://doi.org/10.1373/clinchem.2013.220392.

    Article  CAS  PubMed  Google Scholar 

  26. Keshavan A, Pannee J, Karikari T, Rodriguez J, Ashton N, Nicholas J, Cash D, Coath W, Lane C, Parker T, Lu K, Buchanan S, Keuss S, James S, Murray-Smith H, Wong A, Barnes A, Dickson J, Heslegrave A, Portelius E, Richards M, Fox N, Zetterberg H, Blennow K, Schott J. Population-based blood screening for preclinical Alzheimer’s disease in a British birth cohort at age 70. Brain. 2021;144:434–49. https://doi.org/10.1093/brain/awaa403.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Iino T, Watanabe S, Yamashita K, Tamada E, Hasegawa T, Irino Y, Iwanaga S, Harada A, Noda K, Suto K, Yoshida T. Quantification of amyloid-β in plasma by simple and highly sensitive immunoaffinity enrichment and LC-MS/MS assay. J Appl Lab Med. 2021;6:834–45. https://doi.org/10.1093/jalm/jfaa225.

    Article  PubMed  Google Scholar 

  28. Viodé A, Epelbaum S, Benyounes I, Verny M, Dubois B, Junot C, Fenaille F, Lamari F, Becher F. Simultaneous quantification of tau and α-synuclein in cerebrospinal fluid by high-resolution mass spectrometry for differentiation of Lewy body dementia from Alzheimer’s disease and controls. Analyst. 2019;144:6342–51. https://doi.org/10.1039/C9AN00751B.

    Article  PubMed  Google Scholar 

  29. Chiasserini D, Biscetti L, Eusebi P, Salvadori N, Frattini G, Simoni S, De Roeck N, Tambasco N, Stoops E, Vanderstichele H, Engelborghs S, Mollenhauer B, Calabresi P, Parnetti L. Differential role of CSF fatty acid binding protein 3, α-synuclein, and Alzheimer’s disease core biomarkers in Lewy body disorders and Alzheimer’s dementia. Alzheimers Res Ther. 2017;9:52. https://doi.org/10.1186/s13195-017-0276-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kasai T, Tokuda T, Ishii R, Ishigami N, Tsuboi Y, Nakagawa M, Mizuno T, El-Agnaf OMA. Increased α-synuclein levels in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. J Neurol. 2014;261:1203–9. https://doi.org/10.1007/s00415-014-7334-7.

    Article  CAS  PubMed  Google Scholar 

  31. Kong Y, Chen Z, Wang X, Wang W, Zhang J. Diagnostic utility of cerebrospinal fluid α-synuclein in Creutzfeldt-Jakob disease: a systematic review and meta-analysis. J Alzheimer’s Dis. 2022;89:493–503. https://doi.org/10.3233/JAD-220425.

    Article  CAS  Google Scholar 

  32. Watanabe K, Ishikawa C, Kuwahara H, Sato K, Komuro S, Nakagawa T, Nomura N, Watanabe S, Yabuki M. A new methodology for simultaneous quantification of total-Aβ, Aβx-38, Aβx-40, and Aβx-42 by column-switching LC/MS/MS. Anal Bioanal Chem. 2012;402:2033–42. https://doi.org/10.1007/s00216-011-5648-1.

    Article  CAS  PubMed  Google Scholar 

  33. Lin P, Chen W, Yuan F, Sheng L, Wu Y, Zhang W, Li G, Xu H, Li X. An UHPLC–MS/MS method for simultaneous quantification of human amyloid beta peptides Aβ1-38, Aβ1-40 and Aβ1-42 in cerebrospinal fluid using micro-elution solid phase extraction. J Chromatogr B. 2017;1070:82–91. https://doi.org/10.1016/j.jchromb.2017.10.047.

    Article  CAS  Google Scholar 

  34. Hansson O, Mikulskis A, Fagan AM, Teunissen C, Zetterberg H, Vanderstichele H, Molinuevo JL, Shaw LM, Vandijck M, Verbeek MM, Savage M, Mattsson N, Lewczuk P, Batrla R, Rutz S, Dean RA, Blennow K. The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer’s disease diagnosis: a review. Alzheimer’s Dement. 2018;14:1313–33. https://doi.org/10.1016/j.jalz.2018.05.008.

    Article  Google Scholar 

  35. Forgrave LM, van der Gugten JG, Nguyen Q, DeMarco ML. Establishing pre-analytical requirements and maximizing peptide recovery in the analytical phase for mass spectrometric quantification of amyloid-β peptides 1–42 and 1–40 in CSF. Clin Chem Lab Med. 2021. https://doi.org/10.1515/cclm-2021-0549.

    Article  PubMed  Google Scholar 

  36. Oe T, Ackermann BL, Inoue K, Berna MJ, Garner CO, Gelfanova V, Dean RA, Siemers ER, Holtzman DM, Farlow MR, Blair IA. Quantitative analysis of amyloidβ peptides in cerebrospinal fluid of Alzheimer’s disease patients by immunoaffinity purification and stable isotope dilution liquid chromatography/negative electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 2006;20:3723–35. https://doi.org/10.1002/rcm.2787.

    Article  CAS  PubMed  Google Scholar 

  37. Nakamura A, Kaneko N, Villemagne VL, Kato T, Doecke J, Doré V, Fowler C, Li Q-X, Martins R, Rowe C, Tomita T, Matsuzaki K, Ishii K, Ishii K, Arahata Y, Iwamoto S, Ito K, Tanaka K, Masters CL, Yanagisawa K. High performance plasma amyloid-β biomarkers for Alzheimer’s disease. Nature. 2018;554:249–54. https://doi.org/10.1038/nature25456.

    Article  CAS  PubMed  Google Scholar 

  38. Mawuenyega KG, Kasten T, Sigurdson W, Bateman RJ. Amyloid-beta isoform metabolism quantitation by stable isotope-labeled kinetics. Anal Biochem. 2013;440:56–62. https://doi.org/10.1016/j.ab.2013.04.031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kaneko N, Yamamoto R, Sato T-A, Tanaka K. Identification and quantification of amyloid beta-related peptides in human plasma using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Proc Japan Acad Ser B. 2014;90:104–17. https://doi.org/10.2183/pjab.90.104.

    Article  CAS  Google Scholar 

  40. Kirmess KM, Meyer MR, Holubasch MS, Knapik SS, Hu Y, Jackson EN, Harpstrite SE, Verghese PB, West T, Fogelman I, Braunstein JB, Yarasheski KE, Contois JH. The PrecivityAD™ test: accurate and reliable LC-MS/MS assays for quantifying plasma amyloid beta 40 and 42 and apolipoprotein E proteotype for the assessment of brain amyloidosis. Clin Chim Acta. 2021;519:267–75. https://doi.org/10.1016/j.cca.2021.05.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Shimazaki Y, Takatsu Y. Combined method of immunoaffinity membrane within tubes and MALDI-TOF MS for capturing and analyzing amyloid beta. Appl Biochem Biotechnol. 2015;177:1565–71. https://doi.org/10.1007/s12010-015-1837-2.

    Article  CAS  PubMed  Google Scholar 

  42. Schindler SE, Bollinger JG, Ovod V, Mawuenyega KG, Li Y, Gordon BA, Holtzman DM, Morris JC, Benzinger TLS, Xiong C, Fagan AM, Bateman RJ. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019;93:e1647–59. https://doi.org/10.1212/WNL.0000000000008081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Seino Y, Nakamura T, Harada T, Nakahata N, Kawarabayashi T, Ueda T, Takatama M, Shoji M. Quantitative measurement of cerebrospinal fluid amyloid-β species by mass spectrometry. J Alzheimer’s Dis. 2021;79:573–84. https://doi.org/10.3233/JAD-200987.

    Article  CAS  Google Scholar 

  44. Pannee J, Portelius E, Minthon L, Gobom J, Andreasson U, Zetterberg H, Hansson O, Blennow K. Reference measurement procedure for CSF amyloid beta (Aβ) 1–42 and the CSF Aβ 1–42 /Aβ 1–40 ratio - a cross-validation study against amyloid PET. J Neurochem. 2016;139:651–8. https://doi.org/10.1111/jnc.13838.

    Article  CAS  PubMed  Google Scholar 

  45. Shin YG, Hamm L, Murakami S, Buirst K, Buonarati MH, Cox A, Regal K, Hunt KW, Scearce-Levie K, Watts RJ, Liu X. Qualification and application of a liquid chromatography–tandem mass spectrometric method for the determination of human Aβ1-40 and Aβ1-42 peptides in transgenic mouse plasma using micro-elution solid phase extraction. Arch Pharm Res. 2014;37:636–44. https://doi.org/10.1007/s12272-013-0215-2.

    Article  CAS  PubMed  Google Scholar 

  46. Pannee J, Portelius E, Oppermann M, Atkins A, Hornshaw M, Zegers I, Höjrup P, Minthon L, Hansson O, Zetterberg H, Blennow K, Gobom J. A selected reaction monitoring (SRM)-based method for absolute quantification of Aβ38, Aβ40, and Aβ42 in cerebrospinal fluid of Alzheimer’s disease patients and healthy controls. J Alzheimers Dis. 2013;33:1021–32. https://doi.org/10.3233/JAD-2012-121471.

    Article  CAS  PubMed  Google Scholar 

  47. Lame ME, Chambers EE, Blatnik M. Quantitation of amyloid beta peptides Aβ1–38, Aβ1–40, and Aβ1–42 in human cerebrospinal fluid by ultra-performance liquid chromatography–tandem mass spectrometry. Anal Biochem. 2011;419:133–9. https://doi.org/10.1016/j.ab.2011.08.010.

    Article  CAS  PubMed  Google Scholar 

  48. Souza ID, Anderson JL, Tumas V, Queiroz MEC. Direct coupling of fiber-in-tube solid-phase microextraction with tandem mass spectrometry to determine amyloid beta peptides as biomarkers for Alzheimer’s disease in cerebrospinal fluid samples. Talanta. 2023;254:124186. https://doi.org/10.1016/j.talanta.2022.124186.

  49. Wang R, Sweeney D, Gandy SE, Sisodia SS. The profile of soluble amyloid β protein in cultured cell media. J Biol Chem. 1996;271:31894–902. https://doi.org/10.1074/jbc.271.50.31894.

    Article  CAS  PubMed  Google Scholar 

  50. Vigo-Pelfrey C, Lee D, Keim P, Lieberburg I, Schenk DB. Rapid communication: characterization of β-amyloid peptide from human cerebrospinal fluid. J Neurochem. 1993;61:1965–8. https://doi.org/10.1111/j.1471-4159.1993.tb09841.x.

    Article  CAS  PubMed  Google Scholar 

  51. Lewczuk P, Esselmann H, Meyer M, Wollscheid V, Neumann M, Otto M, Maler JM, Rüther E, Kornhuber J, Wiltfang J. The amyloid-β (Aβ ) peptide pattern in cerebrospinal fluid in Alzheimer’s disease: evidence of a novel carboxyterminally elongated A β peptide. Rapid Commun Mass Spectrom. 2003;17:1291–6. https://doi.org/10.1002/rcm.1048.

    Article  CAS  PubMed  Google Scholar 

  52. Maddalena AS, Papassotiropoulos A, Gonzalez-Agosti C, Signorell A, Hegi T, Pasch T, Nitsch RM, Hock C. Cerebrospinal fluid profile of amyloid β peptides in patients with Alzheimer’s disease determined by protein biochip technology. Neurodegener Dis. 2004;1:231–5. https://doi.org/10.1159/000080991.

    Article  CAS  PubMed  Google Scholar 

  53. Portelius E, Westman-Brinkmalm A, Zetterberg H, Blennow K. Determination of β-amyloid peptide signatures in cerebrospinal fluid using immunoprecipitation-mass spectrometry. J Proteome Res. 2006;5:1010–6. https://doi.org/10.1021/pr050475v.

    Article  CAS  PubMed  Google Scholar 

  54. Portelius E, Tran AJ, Andreasson U, Persson R, Brinkmalm G, Zetterberg H, Blennow K, Westman-Brinkmalm A. Characterization of amyloid β peptides in cerebrospinal fluid by an automated immunoprecipitation procedure followed by mass spectrometry. J Proteome Res. 2007;6:4433–9. https://doi.org/10.1021/pr0703627.

    Article  CAS  PubMed  Google Scholar 

  55. Yu J, Di S, Yu H, Ning T, Yang H, Zhu S. Insights into the structure-performance relationships of extraction materials in sample preparation for chromatography. J Chromatogr A. 2021;1637:461822. https://doi.org/10.1016/j.chroma.2020.461822.

  56. Dias NC, Poole CF. Mechanistic study of the sorption properties of OASIS® HLB and its use in solid-phase extraction. Chromatographia. 2002;56:269–75. https://doi.org/10.1007/BF02491931.

    Article  CAS  Google Scholar 

  57. Salcedo J, Lambert P, Davey L, Lame ME, Dunning C, Chambers EE. Amyloid beta peptides quantification by SPE-LC-MS/MS with automated sample preparation for preclinical research and biomarker discovery. Waters® Application Note. 2019;1–7.

  58. Souza ID, Oliveira IGC, Queiroz MEC Innovative extraction materials for fiber-in-tube solid phase microextraction: a review. Anal Chim Acta. 2021; 1165:238110. https://doi.org/10.1016/j.aca.2020.11.042.

  59. El-Aneed A, Cohen A, Banoub J. Mass spectrometry, review of the basics: electrospray, MALDI, and commonly used mass analyzers. Appl Spectrosc Rev. 2009;44:210–30. https://doi.org/10.1080/05704920902717872.

    Article  CAS  Google Scholar 

  60. Roher AE, Lowenson JD, Clarke S, Wolkow C, Wang R, Cotter RJ, Reardon IM, Zürcher-Neely HA, Heinrikson RL, Ball MJ. Structural alterations in the peptide backbone of beta-amyloid core protein may account for its deposition and stability in Alzheimer’s disease. J Biol Chem. 1993;268:3072–83. https://doi.org/10.1016/S0021-9258(18)53661-9.

    Article  CAS  PubMed  Google Scholar 

  61. Miller DL, Papayannopoulos IA, Styles J, Bobin SA, Lin YY, Biemann K, Iqbal K. Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer′s disease. Arch Biochem Biophys. 1993;301:41–52. https://doi.org/10.1006/abbi.1993.1112.

    Article  CAS  PubMed  Google Scholar 

  62. Dillen L, Cools W, Vereyken L, Timmerman P. A screening UHPLC–MS/MS method for the analysis of amyloid peptides in cerebrospinal fluid of preclinical species. Bioanalysis. 2011;3:45–55. https://doi.org/10.4155/bio.10.163.

    Article  CAS  PubMed  Google Scholar 

  63. Chambers EE, Lame ME, Diehl DM. An improved SPE-LC–MS–MS platform for the simultaneous quantification of multiple amyloid beta peptides in cerebrospinal fluid for preclinical or biomarker discovery. In: LCGC Asia Pacific; 2011.

  64. Pannee J, Gobom J, Shaw LM, Korecka M, Chambers EE, Lame M, Jenkins R, Mylott W, Carrillo MC, Zegers I, Zetterberg H, Blennow K, Portelius E. Round robin test on quantification of amyloid-β 1–42 in cerebrospinal fluid by mass spectrometry. Alzheimer’s Dement. 2016;12:55–9. https://doi.org/10.1016/j.jalz.2015.06.1890.

    Article  Google Scholar 

  65. Yamada T, Sasaki H, Furuya H, Miyata T, Goto I, Sakaki Y. Complementary DNA for the mouse homolog of the human amyloid beta protein precursor. Biochem Biophys Res Commun. 1987;149:665–71. https://doi.org/10.1016/0006-291X(87)90419-0.

    Article  CAS  PubMed  Google Scholar 

  66. Mori H, Takio K, Ogawara M, Selkoe DJ. Mass spectrometry of purified amyloid beta protein in Alzheimer’s disease. J Biol Chem. 1992;267:17082–6. https://doi.org/10.1016/S0021-9258(18)41896-0.

    Article  CAS  PubMed  Google Scholar 

  67. Zakharova NV, Kononikhin AS, Indeykina MI, Bugrova AE, Strelnikova P, Pekov S, Kozin SA, Popov IA, Mitkevich V, Makarov AA, Nikolaev EN. Mass spectrometric studies of the variety of beta-amyloid proteoforms in Alzheimer’s disease. Mass Spectrom Rev. 2022. https://doi.org/10.1002/mas.21775.

    Article  PubMed  Google Scholar 

  68. Portelius E, Bogdanovic N, Gustavsson MK, Volkmann I, Brinkmalm G, Zetterberg H, Winblad B, Blennow K. Mass spectrometric characterization of brain amyloid beta isoform signatures in familial and sporadic Alzheimer’s disease. Acta Neuropathol. 2010;120:185–93. https://doi.org/10.1007/s00401-010-0690-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Shaw LM, Hansson O, Manuilova E, Masters CL, Doecke JD, Li Q-X, Rutz S, Widmann M, Leinenbach A, Blennow K. Method comparison study of the Elecsys® β-Amyloid (1–42) CSF assay versus comparator assays and LC-MS/MS. Clin Biochem. 2019;72:7–14. https://doi.org/10.1016/j.clinbiochem.2019.05.006.

    Article  CAS  PubMed  Google Scholar 

  70. Budelier MM, Bateman RJ. Biomarkers of Alzheimer disease. J Appl Lab Med. 2020;5:194–208. https://doi.org/10.1373/jalm.2019.030080.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Shanthi KB, Krishnan S, Rani P. A systematic review and meta-analysis of plasma amyloid 1–42 and tau as biomarkers for Alzheimer’s disease. SAGE Open Med. 2015;3:205031211559825. https://doi.org/10.1177/2050312115598250.

    Article  Google Scholar 

  72. Janelidze S, Stomrud E, Palmqvist S, Zetterberg H, van Westen D, Jeromin A, Song L, Hanlon D, Tan Hehir CA, Baker D, Blennow K, Hansson O. Plasma β-amyloid in Alzheimer’s disease and vascular disease. Sci Rep. 2016;6:26801. https://doi.org/10.1038/srep26801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Janelidze S, Palmqvist S, Leuzy A, Stomrud E, Verberk IMW, Zetterberg H, Ashton NJ, Pesini P, Sarasa L, Allué JA, Teunissen CE, Dage JL, Blennow K, Mattsson-Carlgren N, Hansson O. Detecting amyloid positivity in early Alzheimer’s disease using combinations of plasma Aβ42/Aβ40 and p-tau. Alzheimer’s Dement. 2022;18:283–93. https://doi.org/10.1002/alz.12395.

    Article  CAS  Google Scholar 

  74. Stanyon HF, Viles JH. Human serum albumin can regulate amyloid-β peptide fiber growth in the brain interstitium. J Biol Chem. 2012;287:28163–8. https://doi.org/10.1074/jbc.C112.360800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kuo Y-M, Kokjohn TA, Kalback W, Luehrs D, Galasko DR, Chevallier N, Koo EH, Emmerling MR, Roher AE. Amyloid-β peptides interact with plasma proteins and erythrocytes: implications for their quantitation in plasma. Biochem Biophys Res Commun. 2000;268:750–6. https://doi.org/10.1006/bbrc.2000.2222.

    Article  CAS  PubMed  Google Scholar 

  76. Rózga M, Kłoniecki M, Jabłonowska A, Dadlez M, Bal W. The binding constant for amyloid Aβ40 peptide interaction with human serum albumin. Biochem Biophys Res Commun. 2007;364:714–8. https://doi.org/10.1016/j.bbrc.2007.10.080.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP process numbers 2017/02147-0, 2019/19485-0, 2020/00126-8), the Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM) (process 465458/2014-9), and CAPES/COFECUB (process 88881.711934/2022-01).

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  1. Departamento de Química, Faculdade de Filosofia Ciências E Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901, Ribeirão Preto, São Paulo, Brazil

    Israel Donizeti de Souza & Maria Eugênia Costa Queiroz

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  1. Israel Donizeti de Souza
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  2. Maria Eugênia Costa Queiroz
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Correspondence to Israel Donizeti de Souza.

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Published in the topical collection Young Investigators in (Bio-)Analytical Chemistry 2023 with guest editors Zhi-Yuan Gu, Beatriz Jurado-Sánchez, Thomas H. Linz, Leandro Wang Hantao, Nongnoot Wongkaew, and Peng Wu.

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de Souza, I.D., Queiroz, M.E.C. Advances in sample preparation and HPLC–MS/MS methods for determining amyloid-β peptide in biological samples: a review. Anal Bioanal Chem 415, 4003–4021 (2023). https://doi.org/10.1007/s00216-023-04631-9

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