Periphery Biomarkers for Objective Diagnosis of Cognitive Decline in Type 2 Diabetes Patients

Yanchao Liu; Shujuan Zhang; Benrong He; Liangkai Chen; Dan Ke; Shi Zhao; Yao Zhang; Wei Wei; Zhipeng Xu; Zihui Xu; Ying Yin; Wen Mo; Yanni Li; Yang Gao; Shihong Li; Weijin Wang; Huiling Yu; Dongqin Wu; Guilin Pi; Tao Jiang; Mingmin Deng; Rui Xiong; Huiyang Lei; Na Tian; Ting He; Fei Sun; Qiuzhi Zhou; Xin Wang; Jinwang Ye; Mengzhu Li; Nan Hu; Guoda Song; Wenju Peng; Chenghong Zheng; Huaqiu Zhang; Jian-Zhi Wang

doi:10.3389/fcell.2021.752753

Periphery Biomarkers for Objective Diagnosis of Cognitive Decline in Type 2 Diabetes Patients

Front Cell Dev Biol. 2021 Oct 20:9:752753. doi: 10.3389/fcell.2021.752753. eCollection 2021.

Authors

Yanchao Liu^{1

2}, Shujuan Zhang¹, Benrong He¹, Liangkai Chen³, Dan Ke¹, Shi Zhao⁴, Yao Zhang⁵, Wei Wei⁴, Zhipeng Xu⁶, Zihui Xu⁴, Ying Yin¹, Wen Mo⁷, Yanni Li⁷, Yang Gao¹, Shihong Li¹, Weijin Wang¹, Huiling Yu¹, Dongqin Wu¹, Guilin Pi¹, Tao Jiang¹, Mingmin Deng¹, Rui Xiong¹, Huiyang Lei¹, Na Tian¹, Ting He¹, Fei Sun¹, Qiuzhi Zhou¹, Xin Wang¹, Jinwang Ye¹, Mengzhu Li¹, Nan Hu¹, Guoda Song¹, Wenju Peng¹, Chenghong Zheng⁸, Huaqiu Zhang², Jian-Zhi Wang^{1

9}

Affiliations

¹ Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Neurosurgery, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Endocrinology, Central Hospital of Wuhan, Wuhan, China.
⁵ Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁶ Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China.
⁷ Health Service Center of Jianghan District, Wuhan, China.
⁸ Department of Endocrinology, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, China.
⁹ Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Abstract

Introduction: Type 2 diabetes mellitus (T2DM) is an independent risk factor of Alzheimer's disease (AD), and populations with mild cognitive impairment (MCI) have high incidence to suffer from AD. Therefore, discerning who may be more vulnerable to MCI, among the increasing T2DM populations, is important for early intervention and eventually decreasing the prevalence rate of AD. This study was to explore whether the change of plasma β-amyloid (Aβ) could be a biomarker to distinguish MCI (T2DM-MCI) from non-MCI (T2DM-nMCI) in T2DM patients. Methods: Eight hundred fifty-two T2DM patients collected from five medical centers were assigned randomly to training and validation cohorts. Plasma Aβ, platelet glycogen synthase kinase-3β (GSK-3β), apolipoprotein E (ApoE) genotypes, and olfactory and cognitive functions were measured by ELISA, dot blot, RT-PCR, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test based on the diluted butanol, and Minimum Mental State Examination (MMSE) test, respectively, and multivariate logistic regression analyses were applied. Results: Elevation of plasma Aβ1-42/Aβ1-40 is an independent risk factor of MCI in T2DM patients. Although using Aβ1-42/Aβ1-40 alone only reached an AUC of 0.631 for MCI diagnosis, addition of the elevated Aβ1-42/Aβ1-40 to our previous model (i.e., activated platelet GSK-3β, ApoE ε4 genotype, olfactory decline, and aging) significantly increased the discriminating efficiency of T2DM-MCI from T2DM-nMCI, with an AUC of 0.846 (95% CI: 0.794-0.897) to 0.869 (95% CI: 0.822-0.916) in the training cohort and an AUC of 0.848 (95% CI: 0.815-0.882) to 0.867 (95% CI: 0.835-0.899) in the validation cohort, respectively. Conclusion: A combination of the elevated plasma Aβ1-42/Aβ1-40 with activated platelet GSK-3β, ApoE ε4 genotype, olfactory decline, and aging could efficiently diagnose MCI in T2DM patients. Further longitudinal studies may consummate the model for early prediction of AD.

Keywords: Alzheimer’s disease; mild cognitive impairment; plasma β-amyloid; platelet glycogen synthase kinase-3β; type 2 diabetes mellitus.

Copyright © 2021 Liu, Zhang, He, Chen, Ke, Zhao, Zhang, Wei, Xu, Xu, Yin, Mo, Li, Gao, Li, Wang, Yu, Wu, Pi, Jiang, Deng, Xiong, Lei, Tian, He, Sun, Zhou, Wang, Ye, Li, Hu, Song, Peng, Zheng, Zhang and Wang.