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

Article type: Research Article

Authors: Tong, Yawei^{a; 1} | Yang, Huan^{a; 1} | Tian, Xiaosheng^a | Wang, Hecheng^a | Zhou, Ting^a | Zhang, Shouzi^b | Yu, Jia^{a; b} | Zhang, Tao^a | Fan, Dongshen^c | Guo, Xiangyang^d | Tabira, Takeshi^f | Kong, Fanjun^{e; *} | Chen, Zheng^{b; *} | Xiao, Weizhong^{c; *} | Chui, Dehua^{a; c; *}

Affiliations: [a] Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education & Ministry of Public Health, Health Science Center, Peking University, Beijing, China | [b] Beijing Geriatric Hospital, Beijing, China | [c] Department of Neurology, Peking University Third Hospital, Beijing, China | [d] Department of Anesthesiology, Peking University Third Hospital, Beijing, China | [e] Affiliated Rehabilitation Hospital of National Research Center for Rehabilitation Technical Aids, Beijing, China | [f] Department of Neurology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan

Correspondence: [*] Correspondence to: Dehua Chui, Neuroscience Research Institute, Peking University Health Science Center, 38 Xueyuan Road, Hai Dian District, 100191 Beijing, China. Tel.: +86 10 8280 2920; Fax: +86 10 8280 5221; E-mail: [email protected].

Note: [1] These authors contributed equally to this paper.

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.

Keywords: High manganese (Mn), cognitive impairment, amyloid-beta (Abeta), Alzheimer's disease (AD), Aβ degradation

DOI: 10.3233/JAD-140534

Journal: Journal of Alzheimer's Disease, vol. 42, no. 3, pp. 865-878, 2014