Hot Off the Press: Novel pathophysiological markers are revealed by iTRAQ-based quantitative clinical proteomics approach in vascular dementia
In research led by collaborator Newman Sze, we used an iTRAQ-2D-LC-MS/MS strategy for quantitative analysis of pooled lysates from the neocortex of 21 pathologically confirmed cases of vascular dementia (VaD) and matched non-neurological controls. A total of 144 differentially perturbed proteins out of 2284 confidently identified proteins (false discovery rate=0.3%) were shortlisted for bioinformatics analysis. Western blot analysis of selected proteins using samples from individual patients (n=10 per group) showed significant increases in the abundance of SOD1 and NCAM and reduced ATP5A in VaD. This suggests a state of hypometabolism and vascular insufficiency along with an inflammatory condition during VaD. Elevation of SOD1 and increasing trend for iron-storage proteins (FTL, FTH1) may be indicative of an oxidative imbalance that is accompanied by an aberrant iron metabolism. The synaptic proteins did not exhibit a generalized decrease in abundance (e.g. syntaxin) in the VaD subjects. This reported proteome offers a reference data set for future basic or translational studies on VaD.
Datta A, Qian J, Chong R, Kalaria RN, Francis P, Lai MK, Chen CP, Sze SK. (This paper).