The Metabolism of Human Soluble Amyloid Precursor Protein Isoforms Is Quantifiable by a Stable Isotope Labeling-Tandem Mass Spectrometry Method
Zakaria, J.A.D.; Bateman, R.J.; Lysakowska, M.; et al.
To better understand the pathophysiological mechanisms of Alzheimer’s disease, Dobrowolska Zakaria et al. developed a novel method to measure the metabolism of amyloid precursor protein (APP) isoforms in vivo. This utilized a stable isotope labeling kinetics (SILK) approach (e.g., with 13C6 L-leucine) together with immunoprecipitation and LC-SRM/MS. Among the findings, the kinetic rates and quantitation of APP isoforms were reproducibly determined in humans for the first time. Although larger sample tests are necessary, evidence suggests that this strategy could help guide clinical trial programs, for example, on therapeutic intervention.