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Alzheimer's disease (AD) is a devastating neurodegenerative disorder that has been predicted to affect 106.2 million people worldwide by 2050. Currently, definitive diagnosis for this disease is given post mortem, and there is a need for biomarker identification to enable earlier diagnosis of this disease. Biomarkers of AD would ideally represent early disease process and will be present in peripheral tissue before cognitive decline develops in this population. Proteomic technologies offer a strategy to undertake such work. In recent times, research in this field has moved away from classical 2-dimensional gel-based proteomics toward more sensitive, non-gel–based proteomic methodologies. In the study presented here, isobaric labeling for relative and absolute quantification was used to assess plasma protein expression in a small group of AD and control samples. Several proteins were identified as being differentially expressed between these 2 populations. Complement 4a plasma protein was identified as increased in AD by isobaric labeling for relative and absolute quantification, and this finding was further validated by Western blotting and enzyme-linked immunosorbent assay. These data suggest that inflammatory processes, which have been shown to be involved in AD pathology in the brain, are also present in plasma.