New Application Note: Simultaneous Quantitation of Multiple Amyloid β Peptides in Cerebrospinal Fluid for Preclinical or Biomarker Discovery on the Improved SPE/LC/MS/MS Platform

Historically, quantification of aβ peptides in biological fluids has relied mainly on the use of immunoassays, such as ELISA. These assays are time consuming and expensive to develop, labor intensive, are subject to cross reactivity, and an individual assay is required for each peptide. In order to meet the throughput requirements and constant flow of demands for new peptide methods in a discovery setting, there is a need for a highly specific yet flexible methodology based on an LC/MS/MS platform. In this work, this platform is coupled with selective sample preparation for the simultaneous quantitation of multiple aβ peptides. This work focuses on methods for the 1-38, 1-40, and 1-42 aβ peptides, in support of preclinical and biomarker discovery studies. Sequence, pI and molecular weight (MW) information for these peptides is shown in the full application on Figure 1.

As strategies emerge for disease modification in Alzheimer’s Disease (AD), the quantification of other aβ species (in addition to aβ 38, 40, and 42) that may be linked to AD pathology may be required. The method described herein shows promise for adaptation to quantify those peptides as well.

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