Abstract
Aggregation of beta amyloid peptides especially Aβ1-42 in amyloid plaques is one of the major neuropathological events in Alzheimer’s disease. This event is normally accompanied by a relative reduction of the concentration of Aβ1-42 in the cerebrospinal fluid (CSF) of patients developing the signs of Alzheimer’s disease. Here, we describe a microchip gel electrophoresis method in a polydimethylsiloxane (PDMS) chip that enables rapid profiling of major Aβ peptides. The method was applied to compare the relative concentration of Aβ1-42 with other Aβ peptides, for example, Aβ 1-40 in CSF. In order to increase the sensitivity of detection, Aβ peptides in the CSF samples were first captured and concentrated using magnetic beads coated with specific anti-Aβ antibodies.
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References
Haass C, Schlossmacher MG, Hung AY et al (1992) Amyloid β-peptide is produced by cultured cells during normal metabolism. Nature 359:322–325
Hardy J, Selkoe DJ (2002) The amyloid hypothesis of alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356
Klein WL, Krafft GA, Finch CE (2001) Targeting small Aβ oligomers: the solution to an Alzheimer’s disease conundrum? Trends Neurosci 24:219–224
Lambert MP, Barlow AK, Chromy BA et al (1998) Diffusible, nonfibrillar ligands derived from Aβ1–42 are potent central nervous system neurotoxins. Proc Natl Acad Sci USA 95:6448–6453
Wiltfang J, Esselmann H, Bibl M et al (2002) Highly conserved and disease-specific patterns of carboxyterminally truncated Aβ peptides 1–37/38/39 in addition to 1–40/42 in Alzheimer’s disease and in patients with chronic neuroinflammation. J Neurochem 81:481–496
Lewczuk P, Wiltfang J (2008) Neurochemical dementia diagnostics: state of the art and research perspectives. Proteomics 8:1292–1301
Jakeway SC, de Mello AJ, Russell EL (2000) Miniaturized total analysis systems for biological analysis. Fresenius J Anal Chem 366:525–539
Chovan T, Guttman A (2002) Microfabricated devices in biotechnology and biochemical processing. Trends Biotechnol 20:116–122
Mohamadi MR, Svobodova Z, Verpillot R et al (2010) Microchip electrophoresis profiling of Aβ peptides in the cerebrospinal fluid of patients with Alzheimer’s disease. Anal Chem 82:7611–7617
Xia Y, Whitesides GM (1998) Soft lithography. Angew Chem Int Ed Engl 37:550–575
Mohamadi MR, Mahmoudian L, Kaji N et al (2007) Dynamic coating using methylcellulose and polysorbate 20 for nondenaturing electrophoresis of proteins on plastic microchips. Electrophoresis 28:830–836
Mohamadi MR, Kaji N, Tokeshi M et al (2007) Online preconcentration by transient isotachophoresis in linear polymer on a poly(methyl methacrylate) microchip for separation of human serum albumin immunoassay mixtures. Anal Chem 79:3667–3672
Verpillot R, Esselmann H, Mohamadi MR et al (2011) Analysis of amyloid-β peptides in cerebrospinal fluid samples by capillary electrophoresis coupled with LIF detection. Anal Chem 83:1696–1703
Jesse S, Brettschneider J, Süssmuth SD et al (2011) Summary of cerebrospinal fluid routine parameters in neurodegenerative diseases. J Neurol 258:1034–1041
Chiari M, Cretich M, Horvath J (2000) New adsorbed coatings for capillary electrophoresis. Electrophoresis 21:909–916
Acknowledgments
This work was supported by European grants LSHB CT 06 037953 (NeuroTAS) and FP7-NMP-09-246513 (NADINE).
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Mohamadi, M.R., Verpillot, R., Taverna, M., Otto, M., Viovy, JL. (2012). Microchip Electrophoresis, with Respect to “Profiling of Aβ Peptides in the Cerebrospinal Fluid of Patients with Alzheimer’s Disease”. In: Kurien, B., Scofield, R. (eds) Protein Electrophoresis. Methods in Molecular Biology, vol 869. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-821-4_14
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DOI: https://doi.org/10.1007/978-1-61779-821-4_14
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