High manganese, a risk for Alzheimer's disease: high manganese induces amyloid-β related cognitive impairment.

Abstract

Excess manganese (Mn) in brain can be neurotoxic, implicated in several neurodegenerative disorders such as sporadic Alzheimer's disease (AD). However, little is known about the altered metal environment including elevated Mn in the progressive cognitive impairment of AD. Indeed, whether high Mn is associated with AD risk remains elusive. In the study, we recruited 40 Chinese elders with different cognitive statuses and investigated concentrations of Mn in whole blood and plasma amyloid-β (Aβ) peptides. Surprisingly, there were significant correlations of Mn with Mini-Mental State Examination score and Clinical Dementia Rating Scale score. In addition, plasma Aβ peptides increased with elevated Mn. Further studies both in vitro and in vivo demonstrated dose-related neurotoxicity and increase of Aβ by Mn treatment, which was probably caused by disrupted Aβ degradation. These data suggested that high Mn may be involved in the progress of AD as an essential pathogenic factor.

• Authors: Yawei Tong, Huan Yang, Xiaosheng Tian, Hecheng Wang, Ting Zhou, Shouzi Zhang, Jia Yu, Tao Zhang, Dongshen Fan, Xiangyang Guo, Takeshi Tabira, Fanjun Kong, Zheng Chen, Weizhong Xiao, Dehua Chui
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 42 Issue 3 Pg. 865-78 ( 2014) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 24961945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Protein Precursor
• PSEN1 protein, human
• Presenilin-1
• Manganese
• L-Lactate Dehydrogenase

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (chemically induced, complications, genetics)
• Amyloid beta-Protein Precursor (genetics)
• Animals
• Brain (metabolism)
• Case-Control Studies
• Cell Line, Tumor
• Cognition Disorders (genetics, metabolism, pathology)
• Exploratory Behavior (drug effects, physiology)
• Extracellular Fluid (drug effects, metabolism)
• Female
• Gene Expression Regulation (drug effects, genetics)
• Humans
• L-Lactate Dehydrogenase (metabolism)
• Male
• Manganese (adverse effects, metabolism)
• Maze Learning (drug effects, physiology)
• Mental Status Schedule
• Mice
• Mice, Transgenic
• Mutation (genetics)
• Neuroblastoma (pathology)
• Presenilin-1 (genetics)