Measurement of Blood Thiamine Metabolites for Alzheimer's Disease Diagnosis
Xiaoli Pan,
Guoqiang Fei,
Jingwen Lu,
Lirong Jin,
Shumei Pan,
Zhichun Chen,
Changpeng Wang,
Shaoming Sang,
Huimin Liu,
Weihong Hu,
Hua Zhang,
Hui Wang,
Zhiliang Wang,
Qiong Tan,
Yan Qin,
Qunying Zhang,
Xueping Xie,
Yong Ji,
Donghong Cui,
Xiaohua Gu,
Jun Xu,
Yuguo Yu,
Chunjiu Zhong
Affiliations
Xiaoli Pan
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
Guoqiang Fei
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
Jingwen Lu
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
Lirong Jin
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
Shumei Pan
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
Zhichun Chen
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
Changpeng Wang
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
Shaoming Sang
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
Huimin Liu
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
Weihong Hu
The Key laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Hua Zhang
The Key laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Hui Wang
Regional Health Service Center of Xujiahui, Xuhui District, Shanghai 200030, China
Zhiliang Wang
Regional Health Service Center of Xujiahui, Xuhui District, Shanghai 200030, China
Qiong Tan
Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China
Yan Qin
Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China
Qunying Zhang
Shanghai Haiwan Hospital, Shanghai 201418, China
Xueping Xie
Department of Geriatrics, Fengcheng Branch, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai 201411, China
Yong Ji
Department of Neurology, Huanhu Hospital, Tianjin 300074, China
Donghong Cui
The Key laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Xiaohua Gu
Department of Neurology, Brain Hospital affiliated to Nanjing medical university, Nanjing 210029, Jiangsu Province, China
Jun Xu
Department of Neurology, Brain Hospital affiliated to Nanjing medical university, Nanjing 210029, Jiangsu Province, China
Yuguo Yu
Center for Computational Systems Biology, School of Life Sciences, Fudan University, Shanghai 200433, China
Chunjiu Zhong
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
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). Aims: 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.
