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In Vivo Stable Isotope Labeling for Quantifying Amyloid-beta Kinetics in Alzheimer's Disease: Is it All in our Head?

Year: 2011
Type: article
Abstract: Mass spectrometry has revolutionized the manner in which we identify, characterize, and quantify proteins. In combination with in vivo stable isotope labeling strategies, mass spectrometry-based analyses can provide valuable information about human amino acid and protein kinetics, protein production (synthesis), and clearance (proteolysis) rates. Dysregulated or imbalanced protein synthesis and degradation rates is the basis for many clinical disorders. These protein kinetic rates can be quantified in vivo and serve to identify potential targets for novel drug therapies. Our group uses an intravenous infusion of 13C6-Leu, cerebral spinal fluid (CSF) sampling, affinity isolation of relevant proteins, and tandem mass spectrometry to quantify 13C6- Leu incorporation and removal rates from CSF amyloid-beta and apolipoproteins in Alzheimer's disease patients. This approach has identified slower amyloid-beta clearance rates as a primary lesion that may explain an accumulation of amyloid plaques in Alzheimer's disease.
Language: English
Open Access status: green
OpenAlex ID: W2293266543
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