New Technique for Measuring Acidic Glycan in Blood Simplifies Schizophrenia Diagnosis

Polysialic acid is a unique acidic glycan predominantly found in brain regions associated with memory and emotion, but it is also present in the bloodstream. Research has shown that blood levels of polysialic acid fluctuate in individuals with psychiatric disorders and even cancer. Notably, patients with schizophrenia have increased concentrations of this glycan.

However, accurately quantifying polysialic acid in the blood has been challenging due to its complex physical and chemical properties. Developing a reliable method for measurement could improve diagnosis and potentially offer insights into disease mechanisms. A new method has now been developed that allows for sensitive and specific detection of polysialic acid in blood samples, offering a possible tool for distinguishing between diseases.

Image: Increased polysialic acid in schizophrenia patients represents a potential diagnostic tool and possible target for treatment (Photo courtesy of 123RF)

Researchers at Nagoya University (Nagoya, Japan) developed a novel diagnostic technique based on a sandwich ELISA format. The method uses a pair of antibodies: a capture antibody and two detection antibodies — one positive and one negative. The negative antibody is a point-mutated version of the positive antibody that retains the same structure but completely loses its ability to bind to polysialic acid. By subtracting the signal from the negative antibody from that of the positive, the technique effectively reduces non-specific binding, a common problem in glycan detection, thereby improving accuracy and sensitivity. This ELISA-based method was designed to specifically recognize the structural features of polysialic acid in blood samples and enable reliable measurement.

The technique was tested on blood samples from patients with schizophrenia and chronic inflammatory demyelinating polyneuropathy. It showed increased levels of polysialic acid in schizophrenia patients but not in the other group, suggesting its usefulness in differentiating between diseases. The results were published in Scientific Reports. The researchers believe this method has broader implications for other conditions, including cancer, where polysialic acid levels are elevated due to substances released by tumor cells. Future work will focus on exploring the mechanisms behind polysialic acid changes across various diseases, which could lead to new therapeutic targets.

“Cancer cells release exosomes and other substances that enter the bloodstream and increase the concentration of polysialic acid,” said corresponding author Chihiro Sato. “Finding out more about the mechanism underlying the increase in blood polysialic acid levels in various diseases could lead to new treatment options for these diseases.”