title: Measurement of Blood Thiamine Metabolites for Alzheimer's Disease Diagnosis.
abstract: BACKGROUND
  Brain glucose hypometabolism is an invariant feature and has significant diagnostic value for Alzheimer's disease. Thiamine diphosphate (TDP) is a critical coenzyme for glucose metabolism and significantly reduced in brain and blood samples of patients with Alzheimer's disease (AD).
  
  
  OBJECTIVE
  To explore the diagnostic value of the measurement of blood thiamine metabolites for AD.
  
  
  METHODS
  Blood TDP, thiamine monophosphate, and thiamine levels were detected using high performance liquid chromatography (HPLC). The study included the exploration and validation phases. In the exploration phase, the samples of 338 control subjects and 43 AD patients were utilized to establish the models for AD diagnosis assayed by receiver operating characteristic (ROC) curve, including the variable γ that represents the best combination of thiamine metabolites and age to predict the possibility of AD. In the validation phase, the values of models were further tested for AD diagnosis using samples of 861 control subjects, 81 AD patients, 70 vascular dementia patients, and 13 frontotemporal dementia patients.
  
  
  RESULTS
  TDP and the γ exhibited significant and consistent values for AD diagnosis in both exploration and validation phases. TDP had 0.843 and 0.837 of the areas under ROC curve (AUCs), 77.4% and 81.5% of sensitivities, and 78.1% and 77.2% of specificities respectively in the exploration and validation phases. The γ had 0.938 and 0.910 of AUCs, 81.4% and 80.2% of sensitivities, and 90.5% and 87.2% of specificities respectively in the exploration and validation phases. TDP and the γ can effectively distinguish AD from vascular dementia (64.3% for TDP, 67.1% for γ) and frontotemporal dementia (84.6% for TDP, 100.0% for γ). Interpretation. The measurement of blood thiamine metabolites by HPLC is an ideal diagnostic test for AD with inexpensive, easy to perform, noninvasive merits.
authors: Department of Neurology, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science & Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors: Xiaoli
authors: X
authors: Pan
authors: Department of Neurology, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science & Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors: Guoqiang
authors: G
authors: Fei
authors: Department of Neurology, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science & Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors: Jingwen
authors: J
authors: Lu
authors: Department of Neurology, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science & Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors: Lirong
authors: L
authors: Jin
authors: Department of Neurology, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science & Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors: Shumei
authors: S
authors: Pan
authors: Department of Neurology, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science & Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors: Zhichun
authors: Z
authors: Chen
authors: Department of Neurology, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science & Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors: Changpeng
authors: C
authors: Wang
authors: Department of Neurology, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science & Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors: Shaoming
authors: S
authors: Sang
authors: Department of Neurology, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science & Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors: Huimin
authors: H
authors: Liu
authors: The Key laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors: Weihong
authors: W
authors: Hu
authors: The Key laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors: Hua
authors: H
authors: Zhang
authors: Regional Health Service Center of Xujiahui, Xuhui District, Shanghai 200030, China.
authors: Hui
authors: H
authors: Wang
authors: Regional Health Service Center of Xujiahui, Xuhui District, Shanghai 200030, China.
authors: Zhiliang
authors: Z
authors: Wang
authors: Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors: Qiong
authors: Q
authors: Tan
authors: Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors: Yan
authors: Y
authors: Qin
authors: Shanghai Haiwan Hospital, Shanghai 201418, China.
authors: Qunying
authors: Q
authors: Zhang
authors: Department of Geriatrics, Fengcheng Branch, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai 201411, China.
authors: Xueping
authors: X
authors: Xie
authors: Department of Neurology, Huanhu Hospital, Tianjin 300074, China.
authors: Yong
authors: Y
authors: Ji
authors: The Key laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors: Donghong
authors: D
authors: Cui
authors: Department of Neurology, Brain Hospital affiliated to Nanjing medical university, Nanjing 210029, Jiangsu Province, China.
authors: Xiaohua
authors: X
authors: Gu
authors: Department of Neurology, Brain Hospital affiliated to Nanjing medical university, Nanjing 210029, Jiangsu Province, China.
authors: Jun
authors: J
authors: Xu
authors: Center for Computational Systems Biology, School of Life Sciences, Fudan University, Shanghai 200433, China. Electronic address: yuyuguo@fudan.edu.cn.
authors: Yuguo
authors: Y
authors: Yu
authors: Department of Neurology, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science & Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China. Electronic address: zhongcj@163.com.
authors: Chunjiu
authors: C
authors: Zhong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D012372:ROC Curve; D012720:Severity of Illness Index; D013831:Thiamine / Q000097:blood / Q000378:metabolism*; D013833:Thiamine Monophosphate; D013835:Thiamine Pyrophosphate
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D013833:Thiamine Monophosphate; D013835:Thiamine Pyrophosphate; D013831:Thiamine
keywords: Alzheimer's disease; Biomarker; Blood; Diagnosis; Thiamine metabolites