PMID- 34746146
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211110
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 9
DP  - 2021
TI  - Periphery Biomarkers for Objective Diagnosis of Cognitive Decline in Type 2 
      Diabetes Patients.
PG  - 752753
LID - 10.3389/fcell.2021.752753 [doi]
LID - 752753
AB  - 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 beta-amyloid (Abeta) 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 Abeta, platelet 
      glycogen synthase kinase-3beta (GSK-3beta), 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 Abeta1-42/Abeta1-40 is an independent risk factor of MCI 
      in T2DM patients. Although using Abeta1-42/Abeta1-40 alone only reached an AUC of 0.631 
      for MCI diagnosis, addition of the elevated Abeta1-42/Abeta1-40 to our previous model 
      (i.e., activated platelet GSK-3beta, ApoE epsilon4 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 Abeta1-42/Abeta1-40 with activated platelet GSK-3beta, ApoE epsilon4 
      genotype, olfactory decline, and aging could efficiently diagnose MCI in T2DM 
      patients. Further longitudinal studies may consummate the model for early 
      prediction of AD.
CI  - Copyright (c) 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.
FAU - Liu, Yanchao
AU  - Liu Y
AD  - 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.
AD  - Department of Neurosurgery, Tongji Medical College, Tongji Hospital, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Zhang, Shujuan
AU  - Zhang S
AD  - 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.
FAU - He, Benrong
AU  - He B
AD  - 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.
FAU - Chen, Liangkai
AU  - Chen L
AD  - 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.
FAU - Ke, Dan
AU  - Ke D
AD  - 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.
FAU - Zhao, Shi
AU  - Zhao S
AD  - Department of Endocrinology, Central Hospital of Wuhan, Wuhan, China.
FAU - Zhang, Yao
AU  - Zhang Y
AD  - Liyuan Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, China.
FAU - Wei, Wei
AU  - Wei W
AD  - Department of Endocrinology, Central Hospital of Wuhan, Wuhan, China.
FAU - Xu, Zhipeng
AU  - Xu Z
AD  - Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China.
FAU - Xu, Zihui
AU  - Xu Z
AD  - Department of Endocrinology, Central Hospital of Wuhan, Wuhan, China.
FAU - Yin, Ying
AU  - Yin Y
AD  - 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.
FAU - Mo, Wen
AU  - Mo W
AD  - Health Service Center of Jianghan District, Wuhan, China.
FAU - Li, Yanni
AU  - Li Y
AD  - Health Service Center of Jianghan District, Wuhan, China.
FAU - Gao, Yang
AU  - Gao Y
AD  - 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.
FAU - Li, Shihong
AU  - Li S
AD  - 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.
FAU - Wang, Weijin
AU  - Wang W
AD  - 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.
FAU - Yu, Huiling
AU  - Yu H
AD  - 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.
FAU - Wu, Dongqin
AU  - Wu D
AD  - 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.
FAU - Pi, Guilin
AU  - Pi G
AD  - 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.
FAU - Jiang, Tao
AU  - Jiang T
AD  - 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.
FAU - Deng, Mingmin
AU  - Deng M
AD  - 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.
FAU - Xiong, Rui
AU  - Xiong R
AD  - 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.
FAU - Lei, Huiyang
AU  - Lei H
AD  - 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.
FAU - Tian, Na
AU  - Tian N
AD  - 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.
FAU - He, Ting
AU  - He T
AD  - 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.
FAU - Sun, Fei
AU  - Sun F
AD  - 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.
FAU - Zhou, Qiuzhi
AU  - Zhou Q
AD  - 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.
FAU - Wang, Xin
AU  - Wang X
AD  - 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.
FAU - Ye, Jinwang
AU  - Ye J
AD  - 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.
FAU - Li, Mengzhu
AU  - Li M
AD  - 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.
FAU - Hu, Nan
AU  - Hu N
AD  - 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.
FAU - Song, Guoda
AU  - Song G
AD  - 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.
FAU - Peng, Wenju
AU  - Peng W
AD  - 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.
FAU - Zheng, Chenghong
AU  - Zheng C
AD  - Department of Endocrinology, Wuhan Hospital of Traditional Chinese Medicine, 
      Wuhan, China.
FAU - Zhang, Huaqiu
AU  - Zhang H
AD  - Department of Neurosurgery, Tongji Medical College, Tongji Hospital, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Wang, Jian-Zhi
AU  - Wang JZ
AD  - 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.
AD  - Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
LA  - eng
PT  - Journal Article
DEP - 20211020
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC8564071
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - mild cognitive impairment
OT  - plasma beta-amyloid
OT  - platelet glycogen synthase kinase-3beta
OT  - type 2 diabetes mellitus
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/11/09 06:00
MHDA- 2021/11/09 06:01
PMCR- 2021/01/01
CRDT- 2021/11/08 06:48
PHST- 2021/08/03 00:00 [received]
PHST- 2021/09/23 00:00 [accepted]
PHST- 2021/11/08 06:48 [entrez]
PHST- 2021/11/09 06:00 [pubmed]
PHST- 2021/11/09 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2021.752753 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2021 Oct 20;9:752753. doi: 10.3389/fcell.2021.752753. 
      eCollection 2021.