High Manganese, A Risk for Alzheimer's Disease: High Manganese Induces Amyloid-β Related Cognitive Impairment

Tong, Yawei; Yang, Huan; Xia, Tian; Wang, Hecheng; Zhou, Ting; Zhang, Shouzi; Yu, Jia; Zhang, Tao; Dong-shen, Fan; Guo, Xiangyang; Tabira, Takeshi; Kong, Fang; Chen, Zheng; Xiao, Weizhong; Chui, Dehua

doi:10.3233/jad-140534

Cited by 100 publications

(61 citation statements)

References 53 publications

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“…The close correlation between Se deficiency and the risk of AD has been shown in previous studies30. However, Mn appeared to have an opposite trend from that reported previously: overexposure to Mn might be involved in the progression of AD as well as other neurodegenerative diseases12474849. Further studies are needed to investigate the relationship between Mn and AD progression.…”

Section: Resultsmentioning

confidence: 51%

Sodium selenate regulates the brain ionome in a transgenic mouse model of Alzheimer’s disease

Zheng

Zhu

Wang

et al. 2016

Sci Rep

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Many studies have shown that imbalance of mineral metabolism may play an important role in Alzheimer’s disease (AD) progression. It was recently reported that selenium could reverse memory deficits in AD mouse model. We carried out multi-time-point ionome analysis to investigate the interactions among 15 elements in the brain by using a triple-transgenic mouse model of AD with/without high-dose sodium selenate supplementation. Except selenium, the majority of significantly changed elements showed a reduced level after 6-month selenate supplementation, especially iron whose levels were completely reversed to normal state at almost all examined time points. We then built the elemental correlation network for each time point. Significant and specific elemental correlations and correlation changes were identified, implying a highly complex and dynamic crosstalk between selenium and other elements during long-term supplementation with selenate. Finally, we measured the activities of two important anti-oxidative selenoenzymes, glutathione peroxidase and thioredoxin reductase, and found that they were remarkably increased in the cerebrum of selenate-treated mice, suggesting that selenoenzyme-mediated protection against oxidative stress might also be involved in the therapeutic effect of selenate in AD. Overall, this study should contribute to our understanding of the mechanism related to the potential use of selenate in AD treatment.

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Section: Resultsmentioning

confidence: 51%

Sodium selenate regulates the brain ionome in a transgenic mouse model of Alzheimer’s disease

Zheng

Zhu

Wang

et al. 2016

Sci Rep

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“…Although advancing age is clearly considered the main risk factor for developing AD [21–23], nutritional factors [24], low levels of physical activity [25, 26], reduced cognitive stimulation [27], socioeconomic status and educational attainment [28–30] are all directly related to AD risk. Furthermore, poor sleep quality [31–33] which is known to positively correlate to early Aβ deposition [34, 35], air pollution [36], smoking [37], intake of metals [38–40], pesticides and insecticides [41, 42] as well as metabolic-related dysfunctions [43, 44] have all been described as possible risk factors.…”

Section: The Ad Research Paradigm Is Failing: Main Facts Supporting Tmentioning

confidence: 99%

Alzheimer disease research in the 21st century: past and current failures, new perspectives and funding priorities

et al. 2016

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Much of Alzheimer disease (AD) research has been traditionally based on the use of animals, which have been extensively applied in an effort to both improve our understanding of the pathophysiological mechanisms of the disease and to test novel therapeutic approaches. However, decades of such research have not effectively translated into substantial therapeutic success for human patients. Here we critically discuss these issues in order to determine how existing human-based methods can be applied to study AD pathology and develop novel therapeutics. These methods, which include patient-derived cells, computational analysis and models, together with large-scale epidemiological studies represent novel and exciting tools to enhance and forward AD research. In particular, these methods are helping advance AD research by contributing multifactorial and multidimensional perspectives, especially considering the crucial role played by lifestyle risk factors in the determination of AD risk. In addition to research techniques, we also consider related pitfalls and flaws in the current research funding system. Conversely, we identify encouraging new trends in research and government policy. In light of these new research directions, we provide recommendations regarding prioritization of research funding. The goal of this document is to stimulate scientific and public discussion on the need to explore new avenues in AD research, considering outcome and ethics as core principles to reliably judge traditional research efforts and eventually undertake new research strategies.

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“…For reviews on selenium and AD, see [99,100]. High manganese induced amyloid-␤ related cognitive impairment [871]. For age-associated changes of brain copper, iron, and zinc in AD see [872].…”

Section: Metal Chelatorsmentioning

confidence: 99%

Cognitive Enhancers (Nootropics). Part 3: Drugs Interacting with Targets other than Receptors or Enzymes. Disease-Modifying Drugs. Update 2014

Froestl

Pfeifer

Muhs

2014

JAD

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Scientists working in the field of Alzheimer's disease and, in particular, cognitive enhancers, are very productive. The review "Drugs interacting with Targets other than Receptors or Enzymes. Disease-modifying Drugs" was accepted in October 2012. In the last 20 months, new targets for the potential treatment of Alzheimer's disease were identified. Enormous progress was realized in the pharmacological characterization of natural products with cognitive enhancing properties. This review covers the evolution of research in this field through May 2014.

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High Manganese, A Risk for Alzheimer's Disease: High Manganese Induces Amyloid-β Related Cognitive Impairment

Cited by 100 publications

References 53 publications

Sodium selenate regulates the brain ionome in a transgenic mouse model of Alzheimer’s disease

Sodium selenate regulates the brain ionome in a transgenic mouse model of Alzheimer’s disease

Alzheimer disease research in the 21st century: past and current failures, new perspectives and funding priorities

Cognitive Enhancers (Nootropics). Part 3: Drugs Interacting with Targets other than Receptors or Enzymes. Disease-Modifying Drugs. Update 2014

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