Molecular imaging of amyloid beta peptides in mouse brain sections using mass spectrometry.

A method is presented for direct spatial analysis of amyloid beta peptides in biological tissue sections. The technique takes advantage of the very high sensitivity of matrix-assisted laser desorption/ionization mass spectrometry and is implemented on a commercial instrument with modifications to only a few components and the software. With this setup, hundreds of molecular images can be generated simultaneously and within just a few minutes. The current features are an instrumental resolution of 50 microm and a sensitivity down to the attomol range. This new technology is applied to the study of amyloid beta peptide distribution in brain sections from mice, showing features reminiscent of Alzheimer's disease.

[1]  S. Gandy,et al.  The profile of soluble amyloid beta protein in cultured cell media. Detection and quantification of amyloid beta protein and variants by immunoprecipitation-mass spectrometry. , 1996, The Journal of biological chemistry.

[2]  M. Stoeckli,et al.  Direct profiling of proteins in biological tissue sections by MALDI mass spectrometry. , 1999, Analytical chemistry.

[3]  M. Staufenbiel,et al.  Electrophoretic Separation of βA4 Peptides (1–40) and (1–42) , 1996 .

[4]  J. Sweedler,et al.  In situ sequencing of peptides from biological tissues and single cells using MALDI-PSD/CID analysis. , 1999, Analytical chemistry.

[5]  B. Sommer,et al.  Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Klaus Dreisewerd,et al.  Direct mass spectrometric peptide profiling and sequencing of nervous tissues to identify peptides involved in male copulatory behavior in Lymnaea stagnalis , 1997 .

[7]  D. Palmer-Toy,et al.  Direct acquisition of matrix-assisted laser Desorption/Ionization time-of-flight mass spectra from laser capture microdissected tissues , 2000, Clinical chemistry.

[8]  A. Proctor,et al.  Direct quantitative analysis of peptides using matrix assisted laser desorption ionization , 1996, Analytical and bioanalytical chemistry.

[9]  A. Proctor,et al.  Selection of internal standards for quantitative analysis by matrix-assisted laser desorption-ionization (MALDI) time-of-flight mass spectrometry , 1997 .

[10]  M. Stoeckli,et al.  Automated mass spectrometry imaging with a matrix-assisted laser desorption ionization time-of-flight instrument , 1999, Journal of the American Society for Mass Spectrometry.

[11]  M. Stoeckli,et al.  Imaging mass spectrometry: A new technology for the analysis of protein expression in mammalian tissues , 2001, Nature Medicine.

[12]  J. Sweedler,et al.  Single-cell MALDI: a new tool for direct peptide profiling. , 2000, Trends in biotechnology.

[13]  R. Caprioli,et al.  Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. , 1997, Analytical chemistry.