The results of the present study are also in keeping with studies in bipolar disorder and depression reporting decreased A2M, IgM, and C4BPA.66 At least some of these proteomic changes may be common to multiple clinical phenotypes, including neurodegenerative disorders, such as Alzheimer disease.67 Rather than considering such changes as biomarkers of individual disorders, phenotypic manifestations may be clinical markers of a variety of overlapping neuroimmune abnormalities that have their origin in combined genetic56,68 and environmental69,70,71,72 factors. This evidence concerns the gene C4BPA and early-onset autosomal dominant Alzheimer disease.