Glycosylation is a frequent co/post-translational modification of proteins which modulates a variety of biological functions. The analysis of N-glycome, i.e. the sugar chains N-linked to asparagine, identified new candidate biomarkers of aging such as N-glycans devoid of galactose residues on their branches, in a variety of human and experimental model systems, such as healthy old people, centenarians and their offspring and caloric restricted mice. These agalactosylated biantennary structures mainly decorate Asn297 of Fc portion of IgG (IgG-G0), and are present also in patients affected by progeroid syndromes and a variety of autoimmune/inflammatory diseases. IgG-G0 exert a pro-inflammatory effect through different mechanisms, including the lectin pathway of complement, binding to Fcγ receptors and formation of autoantibody aggregates. The age-related accumulation of IgG-G0 can contribute to inflammaging, the low-grade pro-inflammatory status that characterizes elderly, by creating a vicious loop in which inflammation is responsible for the production of aberrantly glycosylated IgG which, in turn, would activate the immune system, exacerbating inflammation. Moreover, recent data suggest that the N-glycomic shift observed in aging could be related not only to inflammation but also to alteration of important metabolic pathways. Thus, altered N-glycans are both powerful markers of aging and possible contributors to its pathogenesis.

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the N-glycome profile in serum is gender and age dependent. This should be taken into consideration in the development of serum glycome markers.

We investigated whether blood N-glycan changes can be used as a diagnostic biomarker for Alzheimer disease (AD). We used DNA sequencer-assisted, fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) technology to assay N-glycans in sera from 79 autopsy-confirmed dementia patients and 149 healthy controls. One N-glycan (NA2F) was substantially decreased in AD patients but not in controls. Use of NA2F for discriminating AD between dementia patients and healthy controls showed a diagnostic accuracy of 85.7% +/- 2.8% with 92% specificity and 70% sensitivity. The decrease in the level of NA2F in AD patients compared to non-AD patients was more pronounced in females (p < 0.0001) than in males (p < 0.014). Use of NA2F to differentiate female AD from female non-AD patients reached a diagnostic accuracy of 90.7% +/- 4.8 %. Pearson correlation analysis showed that in female dementia patients, serum NA2F levels were significantly correlated with the cerebrospinal fluid (CSF) beta-amyloid peptide of 42 amino acids (Abeta(1-42)) and tau phosphorylated at threonine 181 (P-tau(181P)) levels, whereas in male dementia patients serum NA2F levels were significantly correlated only with CSF total tau protein (T-tau) level. Thus, we suggest that the serum N-glycan marker might be suitable for longitudinal and follow-up studies.

BackgroundThere is a demand for serum markers for the routine assessment of the progression of liver cancer. We previously found that serum N-linked sugar chains are altered in hepatocellular carcinoma (HCC). Here, we studied glycomic alterations during development of HCC in a rat model.ResultsRat HCC was induced by the hepatocarcinogen, diethylnitrosamine (DENA). N-glycans were profiled using the DSA-FACE technique developed in our laboratory.In comparison with control rats, DENA rats showed a gradual but significant increase in two glycans (R5a and R5b) in serum total N-glycans during progression of liver cirrhosis and cancer, and a decrease in a biantennary glycan (P5). The log of the ratio of R5a to P1 (NGA2F) and R5b to P1 [log(R5a/P1) and log(R5b/P1)] were significantly (p < 0.0001) elevated in HCC rats, but not in rats with cirrhosis or fibrosis or in control rats. We thus propose a GlycoTest model using the above-mentioned serum glycan markers to monitor the progression of cirrhosis and HCC in the DENA-treated rat model. When DENA-treated rats were subsequently treated with farnesylthiosalicyclic acid, an anticancer drug, progression to HCC was prevented and GlycoTest markers (P5, R5a and R5b) reverted towards non-DENA levels, and the HCC-specific markers, log(R5a/P1) and log(R5b/P1), normalized completely. Conclusions: We found an increase in core-α-1,6-fucosylated glycoproteins in serum and liver of rats with HCC, which demonstrates that fucosylation is altered during progression of HCC. Our GlycoTest model can be used to monitor progression of HCC and to follow up treatment of liver tumors in the DENA rat. This GlycoTest model is particularly important because a rapid non-invasive diagnostic procedure for tumour progression in this rat model would greatly facilitate the search for anticancer drugs.