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Alzheimers Res Ther. 2018 Mar 1;10(1):26. doi: 10.1186/s13195-018-0354-2.

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

Sang S1,2, Pan X1,2, Chen Z1,2, Zeng F3, Pan S1,2, Liu H1,2, Jin L1,2, Fei G1,2, Wang C1,2, Ren S4, Jiao F4, Bao W4, Zhou W4, Guan Y4, Zhang Y5, Shi H5, Wang Y3, Yu X6, Wang Y7,8, Zhong C9,10.

Author information

1
Department of Neurology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
2
Institutes of Brain Science & Collaborative Innovation Center for Brain Science, State Key Laboratory of Medical Neurobiology, Fudan University, Room 1105, Mingdao Building, 138 Yixueyuan Road, Shanghai, 200032, China.
3
Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
4
PET Center, Huashan Hospital, Fudan University, Shanghai, 200040, China.
5
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
6
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.
7
Department of Neurology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. wangyun@fudan.edu.cn.
8
Institutes of Brain Science & Collaborative Innovation Center for Brain Science, State Key Laboratory of Medical Neurobiology, Fudan University, Room 1105, Mingdao Building, 138 Yixueyuan Road, Shanghai, 200032, China. wangyun@fudan.edu.cn.
9
Department of Neurology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. zhongcj@163.com.
10
Institutes of Brain Science & Collaborative Innovation Center for Brain Science, State Key Laboratory of Medical Neurobiology, Fudan University, Room 1105, Mingdao Building, 138 Yixueyuan Road, Shanghai, 200032, China. zhongcj@163.com.

Abstract

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-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) was used to evaluate brain glucose metabolism, presented as the rate of 2-[18F]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 11C-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.

KEYWORDS:

Alzheimer’s disease; Amyloid-β; Brain glucose metabolism; Position emission tomography; Thiamine diphosphate

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