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

Quantitative proteomics analysis of cortical samples
of 10 Alzheimer’s disease (AD) brains versus 10 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 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.