Journal Article

Thiamine diphosphate reduction strongly correlates with brain glucose hypometabolism in Alzheimer’s disease, whereas amyloid deposition does not

Sang, Shaoming, Wang, Yanjiang, Pan, Xiaoli, Pan, Shumei, Shi, Hongcheng, Liu, Huimin, Zeng, Fan, Bao, Weiqi, Guan, Yihui, Chen, Zhichun, Ren, Shuhua, Yu, Xiang, Zhong, Chunjiu, Fei, Guoqiang, Zhang, Yiqiu, Wang, Yun, Jin, Lirong, Wang, Changpeng, Jiao, Fangyang, Zhou, Weiyan

2018

Overview

Background The underlying mechanism of brain glucose hypometabolism, an invariant neurodegenerative feature that tightly correlates with cognitive impairment and disease progression of Alzheimer’s disease (AD), remains elusive. Methods Positron emission tomography with 2-[ 18 F]fluoro-2-deoxy- d -glucose (FDG-PET) was used to evaluate brain glucose metabolism, presented as the rate of 2-[ 18 F]fluoro-2-deoxy- d -glucose standardized uptake value ratio (FDG SUVR) in patients with AD or control subjects and in mice with or without thiamine deficiency induced by a thiamine-deprived diet. Brain amyloid-β (Aβ) deposition in patients with clinically diagnosed AD was quantified by performing assays using 11 C-Pittsburgh compound B PET. The levels of thiamine metabolites in blood samples of patients with AD and control subjects, as well as in blood and brain samples of mice, were detected by high-performance liquid chromatography with fluorescence detection. Results FDG SUVRs in frontal, temporal, and parietal cortices of patients with AD were closely correlated with the levels of blood thiamine diphosphate (TDP) and cognitive abilities, but not with brain Aβ deposition. Mice on a thiamine-deprived diet manifested a significant decline of FDG SUVRs in multiple brain regions as compared with those in control mice, with magnitudes highly correlating with both brain and blood TDP levels. There were no significant differences in the changes of FDG SUVRs in observed brain regions between amyloid precursor protein/presenilin-1 and wild-type mice following thiamine deficiency. Conclusions We demonstrate, for the first time to our knowledge, in vivo that TDP reduction strongly correlates with brain glucose hypometabolism, whereas amyloid deposition does not. Our study provides new insight into the pathogenesis and therapeutic strategy for AD.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Alzheimer's disease / Amyloid-β / Biomedical and Life Sciences / Biomedicine / Brain glucose metabolism / Diagnosis / Geriatric Psychiatry / Geriatrics/Gerontology / Myxedema / Neurology / Neurosciences / Position emission tomography / Thiamine / Thiamine diphosphate