Qualitative and quantitative characterization of the amyloid beta peptide (Abeta) population in biological matrices using an immunoprecipitation-LC/MS assay

Journal of Neuroscience Methods
Michael J FordDieter M Drexler

Abstract

Targeting the metabolism of amyloid beta peptides (Abeta) is currently the leading experimental approach to treatment of Alzheimer's disease (AD). Described here is an immunoprecipitation-liquid chromatography/mass spectrometry (ip-LC/MS) assay to simultaneously characterize and quantitate different forms of Abeta in biological samples. The 4G8 antibody, specific for the 17-24 amino acid epitope of Abeta was employed to selectively isolate Abeta from in vitro samples for subsequent LC-MS analysis. A high resolution accurate mass hybrid linear ion trap-Orbitrap, LTQ-Orbitrap mass spectrometer was used to identify forms of 12 Abeta in H4-APP751 swe cell extracts based on ab initio calculations, accurate mass measurements, isotopic modeling and by de novo peptide sequencing using tandem mass spectrometry. The quantitative LC-MS analysis was performed on a linear ion trap mass spectrometer, LTQ, in full scan mode, this mode of operation enables sensitive detection levels and post-acquisition data mining for different forms of Abeta for quantitative assessment. Dosing studies with three known inhibitors of Abeta production, sulindac sulfide (SSide), BMS-299897 ('897) and compound W (CW) are reported to demonstrate the utility and an...Continue Reading

References

Nov 5, 2002·Annual Review of Pharmacology and Toxicology·Dennis J Selkoe, Dale Schenk
Mar 15, 2003·The Journal of Biological Chemistry·Yasuko TakahashiTakeshi Iwatsubo
Aug 6, 2004·Nature·Mark P Mattson
Jan 27, 2005·Biochemical Pharmacology·Jeffery J AndersonSteven L Wagner
Jan 18, 2006·Analytical Chemistry·John R YatesVlad Zabrouskov
Apr 4, 2006·Analytical Chemistry·Alexander MakarovStevan Horning
Jun 27, 2006·Nature Medicine·Randall J BatemanDavid M Holtzman
Aug 22, 2006·The Journal of Pharmacology and Experimental Therapeutics·Thomas A LanzJoel B Schachter
Mar 27, 2007·Journal of the American Society for Mass Spectrometry·Randall J BatemanKevin E Yarasheski
Apr 1, 1995·Journal of the American Society for Mass Spectrometry·M W SenkoF W McLaffertycor

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Citations

May 27, 2010·Analytical and Bioanalytical Chemistry·Henning WibergJohan Roeraade
Feb 1, 2013·International Journal of Proteomics·John E Hale
Aug 15, 2012·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Alan Hb WuKara L Lynch
Aug 8, 2008·Mass Spectrometry Reviews·Richard H PerryRobert J Noll
Aug 15, 2014·Acta Neuropathologica·Andrew D WattLuke A Miles
May 24, 2008·The Journal of Pharmacology and Experimental Therapeutics·Jere E MeredithCharles F Albright
Oct 30, 2019·Critical Reviews in Clinical Laboratory Sciences·Bhavana VeerabhadrappaSylvain Lehmann
Nov 28, 2012·Clinical Chemistry and Laboratory Medicine : CCLM·Sylvain LehmannUNKNOWN IFCC Working Group on Clinical Quantitative Mass Spectrometry Proteomics (WG-cMSP)
Apr 19, 2011·Mass Spectrometry Reviews·Giuseppe Grasso
Jan 13, 2010·Analytical Chemistry·Daniel P MagparangalanRichard A Yost

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