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

Frontiers in Cell and Developmental Biology

Jian-Zhi Wang¹  Shi Zhao²  Wei Wei²  Zihui Xu²  Chenghong Zheng³  Zhipeng Xu⁴  Huaqiu Zhang⁵  Yanchao Liu⁵  Liangkai Chen⁶  Yanni Li⁷  Wen Mo⁷  Yao Zhang⁸  Ying Yin⁹  Huiyang Lei⁹  Benrong He⁹  Mingmin Deng⁹  Dongqin Wu⁹  Na Tian⁹  Guilin Pi⁹  Yang Gao⁹  Weijin Wang⁹  Qiuzhi Zhou⁹  Tao Jiang⁹  Shihong Li⁹  Jinwang Ye⁹  Fei Sun⁹  Guoda Song⁹  Nan Hu⁹  Xin Wang⁹  Shujuan Zhang⁹  Wenju Peng⁹  Dan Ke⁹  Rui Xiong⁹  Ting He⁹  Huiling Yu⁹  Mengzhu Li⁹ 

[1] Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China;Department of Endocrinology, Central Hospital of Wuhan, Wuhan, China;Department of Endocrinology, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, China;Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China;Department of Neurosurgery, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China;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;Health Service Center of Jianghan District, Wuhan, China;Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;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;

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

DOI  :  10.3389/fcell.2021.752753

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown