Frontiers in Cell and Developmental Biology (Oct 2021)
Periphery Biomarkers for Objective Diagnosis of Cognitive Decline in Type 2 Diabetes Patients
- Yanchao Liu,
- 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,
- Jian-Zhi Wang
Affiliations
- Yanchao Liu
- 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
- Yanchao Liu
- Department of Neurosurgery, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
- Shujuan Zhang
- 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
- Benrong He
- 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
- Liangkai Chen
- 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
- Dan Ke
- 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
- Shi Zhao
- Department of Endocrinology, Central Hospital of Wuhan, Wuhan, China
- Yao Zhang
- Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Wei Wei
- Department of Endocrinology, Central Hospital of Wuhan, Wuhan, China
- Zhipeng Xu
- Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Zihui Xu
- Department of Endocrinology, Central Hospital of Wuhan, Wuhan, China
- Ying Yin
- 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
- Wen Mo
- Health Service Center of Jianghan District, Wuhan, China
- Yanni Li
- Health Service Center of Jianghan District, Wuhan, China
- Yang Gao
- 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
- Shihong Li
- 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
- Weijin Wang
- 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
- Huiling Yu
- 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
- Dongqin Wu
- 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
- Guilin Pi
- 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
- Tao Jiang
- 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
- Mingmin Deng
- 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
- Rui Xiong
- 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
- Huiyang Lei
- 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
- Na Tian
- 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
- Ting He
- 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
- Fei Sun
- 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
- Qiuzhi Zhou
- 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
- Xin Wang
- 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
- Jinwang Ye
- 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
- Mengzhu Li
- 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
- Nan Hu
- 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
- Guoda Song
- 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
- Wenju Peng
- 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
- Chenghong Zheng
- Department of Endocrinology, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, China
- Huaqiu Zhang
- Department of Neurosurgery, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
- Jian-Zhi Wang
- 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
- Jian-Zhi Wang
- Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
- DOI
- https://doi.org/10.3389/fcell.2021.752753
- Journal volume & issue
-
Vol. 9
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
- type 2 diabetes mellitus
- Alzheimer’s disease
- mild cognitive impairment
- plasma β-amyloid
- platelet glycogen synthase kinase-3β