Dataset Information

Enhanced Activities of Blood Thiamine Diphosphatase and Monophosphatase in Alzheimer's Disease.

ABSTRACT:

Background

Thiamine metabolites and activities of thiamine-dependent enzymes are impaired in Alzheimer's disease (AD).

Objective

To clarify the mechanism for the reduction of thiamine diphosphate (TDP), an active form of thiamine and critical coenzyme of glucose metabolism, in AD.

Methods

Forty-five AD patients clinically diagnosed and 38 age- and gender-matched control subjects without dementia were voluntarily recruited. The contents of blood TDP, thiamine monophosphate (TMP), and thiamine, as well as the activities of thiamine diphosphatase (TDPase), thiamine monophosphatase (TMPase), and thiamine pyrophosphokinase (TPK), were assayed by high performance liquid chromatography.

Results

Blood TDP contents of AD patients were significantly lower than those in control subjects (79.03 ± 23.24 vs. 127.60 ± 22.65 nmol/L, P<0.0001). Activities of TDPase and TMPase were significantly enhanced in AD patients than those in control subjects (TDPase: 1.24 ± 0.08 vs. 1.00 ± 0.04, P < 0.05; TMPase: 1.22 ± 0.04 vs. 1.00 ± 0.06, P < 0.01). TPK activity remained unchanged in AD as compared with that in control (0.93 ± 0.04 vs. 1.00 ± 0.04, P > 0.05). Blood TDP levels correlated negatively with TDPase activities (r = -0.2576, P = 0.0187) and positively with TPK activities (r = 0.2426, P = 0.0271) in all participants.

Conclusion

Enhanced TDPase and TMPase activities may contribute to the reduction of TDP level in AD patients. The results imply that an imbalance of phosphorylation-dephosphorylation related to thiamine and glucose metabolism may be a potential target for AD prevention and therapy.

SUBMITTER: Pan X

PROVIDER: S-EPMC5218390 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Enhanced Activities of Blood Thiamine Diphosphatase and Monophosphatase in Alzheimer's Disease.

Pan Xiaoli X Sang Shaoming S Fei Guoqiang G Jin Lirong L Liu Huimin H Wang Zhiliang Z Wang Hui H Zhong Chunjiu C

PloS one 20170106 1

<h4>Background</h4>Thiamine metabolites and activities of thiamine-dependent enzymes are impaired in Alzheimer's disease (AD).<h4>Objective</h4>To clarify the mechanism for the reduction of thiamine diphosphate (TDP), an active form of thiamine and critical coenzyme of glucose metabolism, in AD.<h4>Methods</h4>Forty-five AD patients clinically diagnosed and 38 age- and gender-matched control subjects without dementia were voluntarily recruited. The contents of blood TDP, thiamine monophosphate ( ...[more]

PMID: 28060825

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Project description:Alzheimer's disease (AD) is a neurodegenerative and progressive disorder that results in brain malfunctions. Resting-state (RS) functional magnetic resonance imaging (fMRI) techniques have been successfully applied for quantifying brain activities of both Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients. Region-based approaches are widely utilized to classify patients from cognitively normal subjects (CN). Nevertheless, region-based approaches have a few limitations, reproducibility owing to selection of disease-specific brain regions, and heterogeneity of brain activities during disease progression. For coping with these issues, network-based approaches have been suggested in the field of molecular bioinformatics. In comparison with individual gene-based approaches, they acquired more accurate results in diverse disease classification, and reproducibility was confirmed by replication studies. In our work, we applied a similar methodology integrating brain pathway information into pathway activity inference, and permitting classification of both aMCI and AD patients based on pathway activities rather than single region activities.After aggregating the 59 brain pathways from literature, we estimated brain pathway activities by using exhaustive search algorithms between patients and cognitively normal subjects, and identified discriminatory pathways according to disease progression. We used three different data sets and each data set consists of two different groups. Our results show that the pathway-based approach (AUC = 0.89, 0.9, 0.75) outperformed the region-based approach (AUC = 0.69, 0.8, 0.68). Also, our approach provided enhanced diagnostic power achieving higher accuracy, sensitivity, and specificity (pathway-based approach: accuracy = 83%; sensitivity = 86%; specificity = 78%, region-based approach: accuracy = 74%; sensitivity = 78%; specificity = 76%).We proposed a novel method inferring brain pathway activities for disease classification. Our approach shows better classification performance than region-based approach in four classification models. We expect that brain pathway-based approach would be helpful for precise classification of brain disorders, and provide new opportunities for uncovering disrupted brain pathways caused by disease. Moreover, discriminatory pathways between patients and cognitively normal subjects may facilitate the interpretation of functional alterations during disease progression.

Dataset Information

Enhanced Activities of Blood Thiamine Diphosphatase and Monophosphatase in Alzheimer's Disease.

Background

Objective

Methods

Results

Conclusion

Publications

Enhanced Activities of Blood Thiamine Diphosphatase and Monophosphatase in Alzheimer's Disease.

Similar Datasets

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