Biomarkers Help Diagnose Mild Cognitive Impairment in Diabetics

Alzheimer's disease is the most common cause of senile dementia, and the prevalence is increasing with population aging and even when the clinical diagnosis of Alzheimer's disease is made, it is generally too late to be curable.

Type 2 diabetes mellitus (T2DM) is also an age-associated disorder, and the patients with T2DM show a significantly increased risk to suffer from Alzheimer's disease. Biomarkers that can diagnose or predict conversion of T2DM into Alzheimer's disease would make it possible to start an early intervention, and eventually reduces the incidence of Alzheimer's disease.

Scientists at the Huazhong University of Science and Technology (Wuhan, China) and their colleagues recruited 646 T2DM patients from January 2012 to May 2015 from five hospitals. Patients in each set were randomly divided into two groups: T2DM without mild cognitive impairment (MCI) (termed T2DM-nMCI) or with MCI (termed T2DM-MCI). Glycogen synthase kinase-3β (GSK-3β) activity in platelets, ApoE genotypes in leucocytes and the olfactory function were detected by Western/dot blotting.

For biochemical indicators, all participants were asked to measure fasting blood glucose, postprandial blood glucose, serum insulin, hemoglobinA1c (HbA1c) and serum magnesium, the next morning. On receipt, serum, leukocytes and platelet samples were separated from EDTA whole blood by centrifugation, which were collected and stored at -80 °C until analysis. The total GSK-3β (tGSK-3β) and serine-9 phosphorylated GSK-3β (pS9GSK-3β, the inactive form of the kinase) in serum or platelet were measured by ELISA (Cusabio Biotech Co., Ltd.; Wuhan, China), Western blotting or dot blotting. In addition, the biochemical activity of GSK-3β in platelet was measured by using enzyme activity assay kit.

The scientists found no significant differences for sex, T2DM years, hypertension, hyperlipidemia, coronary disease, complications, insulin treatment, HbA1c, ApoE ε2, ApoE ε3, tGSK3β and pS9GSK3β between the two groups. They did find that that activation of the peripheral circulating GSK-3β, expression of ApoE ε4, dysfunction of the olfactory function, and aging are diagnostic for the mild cognitive impairment in T2DM patients, and combination of these factors can significantly improve the diagnostic accuracy. They also developed a simple protocol for measuring the total and the inactivated form of GSK-3β in human platelets. As the method is simple and easy to operate with low cost and good repeatability, it is suitable for application in clinical laboratories.

Jian-Zhi Wang, PhD, a professor and senior author of the study, said, “Although we have designed training set and validation set respectively to assure the correlation of cognitive impairments with the biomarkers, further longitudinal studies are needed to confirm how informative these biomarkers in predicting the conversion of T2DM into Alzheimer's disease.” The study was published on February 13, 2016, in the journal EbioMedicine.

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Huazhong University of Science and Technology
Cusabio Biotech