Candidate blood proteome markers of Alzheimer's disease onset and progression: a systematic review and replication study.
The objective of this study was to search for biological markers associated with Alzheimer's disease (AD). Plasma specimens obtained from ten pathologically diagnosed AD patients and ten non-demented (ND) control subjects were analyzed by a combination of 2-DE and MS. This strategy allowed us to identify six plasma proteins (alpha-1-antitrypsin, vitamin D-binding protein, inter-alpha-trypsin inhibitor family heavy chain-related protein, apolipoprotein J precursor, cAMP-dependent protein kinase catalytic subunit alpha 1, and an orf) whose 2-DE spot densities were different between the AD and ND groups. Due to their involvements in AD amyloid plaque formation, the plasma concentrations of alpha-1-antitrypsin and apolipoprotein J were further validated using either ELISA or Western blot. The results revealed that the plasma levels of alpha-1-antitrypsin in AD were higher than those of controls, confirming the 2-DE findings. However, no difference in total apolipoprotein J concentration was observed between the AD and ND groups. Considering the difference in resolving power to differentially quantitate protein isoforms provided by 2-DE and Western blot, 2-DE analysis combined with MS protein identification offers distinctive advantages when a disease-related protein isoform-specific variance is investigated.