https://onlinelibrary.wiley.com/doi/10.1111/1753-0407.13470

Both the activation of glycogen synthase kinase-3β (GSK-3β) and the presence of ApoE ε4 genotype have been found to respectively correlate with cognitive decline in patients with type 2 diabetes mellitus (T2DM), who further show a high incidence of developing Alzheimer's disease. However, the relationship between ApoE ε4 and GSK-3β in the cognitive impairment of T2DM patients remains unclear. 

Prof. Jian-Zhi Wang's team in HUST, in collaboration with us, revealed that T2DM patients with ApoE ε4 but not ApoE ε2 haplotype showed poorer cognitive function and elevated platelet GSK-3β activity, when using ApoE ε3 as reference. The elevation of GSK-3β activity was positively correlated the diabetes duration, as well as plasma glycated hemoglobin (HbA1c) and glucose levels. Moreover, correlation and regression analysis also revealed significant pairwise correlations among GSK-3β activity, ApoE gene polymorphism and cognitive function. Lastly, using Baron and Kenny modeling, we unveiled a mediative role of GSK-3β activity between ApoE ε4 and cognitive impairment.

These results suggest that GSK-3β inhibitors as promising drugs for preserving cognitive function in T2DM patients, especially to those with ApoE ε4 genotype.

Dr. Gao Yang and Yu Haitao are co-first authors of this article, Prof. Wang Jian-Zhi and Zheng Jie are co-corresponding authors.