Label-Free Quantitative LC–MS Proteomics of Alzheimer’s Disease and Normally Aged Human Brains

Abstract

Quantitative proteomics analysis of cortical samples of ten Alzheimer's disease (AD) brains versus ten normally aged brains was performed by following the accurate mass and time tag (AMT) approach with the high resolution LTQ Orbitrap mass spectrometer. More than 1400 proteins were identified and quantitated. A conservative approach of selecting only the consensus results of four normalization methods was suggested and used. A total of 197 proteins were shown to be significantly differentially abundant (p-values<0.05, corrected for multiplicity of testing) in AD versus control brain samples. Thirty seven of these proteins were reported as differentially abundant or modified in AD in the previous proteomics and transcriptomics publications. The rest to the best of our knowledge are new. Mapping of the discovered proteins with bioinformatic tools revealed significant enrichment with differentially abundant proteins of pathways and processes known to be important in AD, including signal transduction, regulation of protein phosphorylation, immune response, cytoskeleton organization, lipid metabolism, energy production, and cell death.

Neurodegeneration and Alzheimer's disease (AD). What Can Proteomics Tell Us About the Alzheimer's Brain?

“…Primary references are cited next to the protein. In List 2 are proteins that were identified and published in (73) that coincided with a similar finding in at least one other study (37,73) and also proteins that are common to List 3 (see Fig. 1).…”

Salinity-induced activation of the myo-inositol biosynthesis pathway in tilapia gill epithelium

“…Therefore, studies investigating how tilapia respond to such hypersaline conditions are not only informative for dissecting the mechanisms of euryhalinity and extreme osmotic stress tolerance, but they are also relevant from an ecophysiological perspective. The present study utilizes a targeted proteomics approach consisting of online liquid chromatography-tandem mass spectrometry (LC-MS/MS) and utilization of accurate mass and time tags (AMT) (Cutillas and Vanhaesebroeck, 2007;Andreev et al, 2012;Matzke et al, 2013) to quantify both enzymes of the MIB pathway in gills of Mozambique tilapia [Oreochromis mossambicus (Peters 1852)] after exposure to different types of salinity stress. Changes in protein abundance in response to environmental stress can occur as a result of increasing the corresponding mRNA to increase translation (Gracey et al, 2001), but may also be a result of protein (de)stabilization and altered rates of turnover (Flick and Kaiser, 2012).…”

Neuroproteomics tools in clinical practice

“…For neuroproteomics studies, label-free quantification has been recently used to analyze changed protein expression e.g. in brain tissue of AD patients [68] and spinal cord tissue of ALS patients [69].…”

“…Label free quantitative proteomics was used to investigate the protein expression in the brain cortex [68,83] and substantia nigra [84] of AD patients, leading to the identification of 197, 13 and 19 differentially expressed proteins, respectively.…”