with depression. Although there are no previous reports linking clusterin to depression, our finding that clusterin is increased in subjects with depression ties in with the growing evidence on inflammatory markers as potential Analysis of plasma clusterin Clusterin plasma levels were measured in duplicate using a Human Clusterin ELISA that has previously been used in numerous publications. Spiking and recovery experiments showed 102% recovery and inter-assay variability was less than 9%. Quality control values were within expected range. Statistical analysis Inter-group differences in plasma clusterin were identified using a nonparametric Kruskal-Wallis test BIBW 2992 followed by a Mann-Whitney test on each pair of groups, adjusting the p-value using the Bonferroni method. Linear regression analyses were used to investigate associations between plasma clusterin and MiniMental-State Examination in all clinical groups, whereas correlations between plasma clusterin and cerebrospinal fluid biomarkers Ab42, total tau and phosphorylated tau were only performed in 31 AD samples. Results In table 1 we present the demographic data and the plasma clusterin levels. Clusterin plasma levels did not differ between controls and patients with AD, DLB, VaD, FTD or PDD. A small, but significantly different increase in plasma clusterin was observed in patients with depression when compared to controls, AD, DLB, and FTD subjects . Controls Mean age, years % of females MMSE Clusterin, mg/ml 74 64 16722652 2960.1 33.3 AD 75 71 2160.4 33.3 DLB 75 68 2160.89 33.2 Depr. 59 50 2860.4 38.6 FTD 61 41 2261.8 33.3 VaD 76 68 2260.9 35.0 PDD 72 42 2061.9 34.1 p,0.001 when comparing Depr. with controls, AD, DLB or FTD using KruskalWallis one-way analysis of variance by ranks followed by Mann-Whitney U tests. doi:10.1371/journal.pone.0050237.t001 2 Plasma Clusterin in AD markers for depression. Several studies consistently report that subjects with depression demonstrate increased plasma levels of a variety inflammatory biomarkers when compared with nondepressed subjects,. Interestingly, increased levels of the complement factors C3 and C4 25137254 have been observed in patients with depression compared to controls,. It would, therefore, be interesting to 
investigate whether the increased clusterin levels that we observe in depressed subjects are linked to increased complement activation. Although the finding of increased plasma clusterin in depression fits in with the hypothesis of depression being an inflammatory disorder, it is necessary to replicate this finding in a different and larger cohort. created optimism for finding easily accessible and detectable disease-specific markers. However, our results suggest that plasma clusterin levels have no diagnostic value for AD. In our study, plasma clusterin was significantly elevated in depressed subject compared to controls and several dementias, adding to the evidence of involvement of inflammation in depression. Monoclonal antibodies have been used with increasing frequency to treat a wide spectrum of human diseases, including heart disease, infections and immune disorders. The mAb based immunotherapies are now standard of care in an increasing number of human cancers including Erb2+ breast cancer, NonHodgkin’s Lymphoma, colon cancer and others. Since 2001, human mAbs developed through recombinant DNA techniques have constituted the largest number entering clinical study. This shift, toward de novo human mAb isolation and their clinical use, is
