Altered Serum Glycomics in Alzheimer Disease: A Potential Blood Biomarker?

Abstract

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.

Cell Surface-Specific N-Glycan Profiling in Breast Cancer

“…It has been widely accepted as a biomarker screening approach in cancer and other disease research. For instance, DSA-FACE has been applied to identify serum protein biomarkers for liver fibrosis (GlycoFibroTest) [20], hepatic cirrhosis (GlycoCirrohTest) [35], hepatocellular cancer (GlycoHCCTest) [34], Alzheimer’s disease [17] and colorectal cancer (CRCglycoA/B) [27]. However, to our knowledge, there has been no previous report on membrane protein N-glycan profiling from tissues or cell lines obtained with DSA-FACE, which could be a limitation of its further use in glycomics.…”

Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease

“…In addition, lectin studies have shown decreased binding of WGA (wheat germ agglutinin), a lectin, that binds to sialic acid residues, in CSF of AD patients [150, 151]. Other than sialylated and bisecting N- glycans, reduction of NA2F, a core-fucosylated biantennary terminal galactose N -glycan structure, has been reported in AD compared to healthy controls, and it has been suggested to serve as suitable serum N -glycan marker for AD [152]. …”

A comprehensive glycome profiling of Huntington's disease transgenic mice

“…Understanding the glycosylation pattern of N-, O-, and glycosphingolipids (GSL)-glycans, which is affected by either genetic or environmental cellular stressors, is a promising step towards an easy prognosis of disease progression. Either serum or cerebrospinal fluid (CSF) specimens from a human with neurodegeneration and aging are validated for biomarker detection [13][14][15]. Glycosylation is the most prevalent post-translational modification (PTM) of proteins in higher organisms essential to modulate a wide range of protein and lipid functions within or on extracellular surfaces of the cell.…”