APOE and Alzheimer disease: To deal with these limitations, cross-sectional screening and longitudinal follow-up studies have been carried out to search periphery biomarkers for pre-clinical diagnosis of AD in high-risk populations, such as those at the old age or with T2DM. By dividing the T2DM patients into two groups (i.e., with or without MCI), we found that the T2DM-MCI patients showed GSK-3β activation with olfactory dysfunction and APOE4 genetype compared with T2DM-nMCI populations [21, 25].