This work focuses on the development of UPLC, MS, and selective SPE sample preparation methods for the 1-38, 1-40, and 1-42 fragments of APP, in support of preclinical studies. Sequence, pI and molecular weight (MW) information for these peptides is shown in Figure 1. The use of a single, high throughput assay for multiple aβ peptides- without time consuming immunoprecipitation steps was developed and validated. The speed, selectivity, and specificity of this technique for simultaneously quantitating multiple aβ peptides in CSF are demonstrated. As strategies emerge for disease modification in AD, the quantification of multiple aβ species (in addition to aβ 38, 40 and 42) that may be linked to AD pathology may help to offer more insight into this disease and its progression. The method described herein shows promise for adaptation to quantitate those peptides as well.
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